Guiding synovial inflammation by macrophage phenotype modulation: An in vitro study towards a therapy for osteoarthritis

Objective: The aims of this study were to modulate inflammation in synovial explants with the compounds: dexamethasone, rapamycin, bone morphogenetic protein 7 (BMP-7) and pravastatin, and to investigate the mod

The Effect of Biomaterials Used for Tissue Regeneration Purposes on Polarization of Macrophages

Activation of macrophages is critical in the acute phase of wound healing after implantation of surgical biomaterials. To understand the response of macrophages, they are often cultured in vitro on biomaterials. Since a wide range of biomaterials is currently used in the clinics, we undertook a systematic review of the macrophage polarization in response to these different surgical biomaterials in vitro. Beside the chemistry, material characteristics such as dimension, pore size, and surface topography are of great influence on the response of macrophages. The macrophage response also appears to depend on the differences in sterilization techniques that induce lasting biochemical changes or residues of chemicals and their byproducts used for sterilization. Regarding tissue-based biomaterials, macrophages on human or porcine dermis, strongly cross-linked by chemicals elicit in general a proinflammatory response with higher amounts of proinflammatory cytokines. Synthetic biomaterials such as polyethylene, polyethylene terephthalate (PET) + polyacrylamide (PAAm), PET + sodium salt of poly(acrylic acid) (PAANa), perfluoropolyether (PFPE) with large posts, PEG-g-PA, and polydioxanone (PDO) always appear to elicit an anti-inflammatory response in macrophages, irrespective of origin of the macrophages, for example, buffy coats or full blood. In conclusion, in general in vitro models contribute to evaluate the foreign body reaction on surgical biomaterials. Although it is difficult to simulate complexity of host response elicited by biomaterials, after their surgical implantation, an in vitro model gives indications of the initial foreign body response and allows the comparison of this response between biomaterials

Development and characterisation of cytocompatible polyester substrates with tunable mechanical properties and degradation rate

Although it has been repeatedly indicated the importance to develop implantable devices and cell culture substrates with tissue-specific rigidity, current commercially available products, in particular cell culture substrates, have rigidity values well above most tissues in the body. Herein, six resorbable polyester films were fabricated using compression moulding with a thermal presser into films with tailored stiffness by appropriately selecting the ratio of their building up monomers (e.g. lactide, glycolide, trimethylene carbonate, dioxanone, ε-caprolactone). Typical NMR and FTIR spectra were obtained, suggesting that the fabrication process did not have a negative effect on the conformation of the polymers. Surface roughness analysis revealed no apparent differences between the films as a function of polymer composition. Subject to polymer composition, polymeric films were obtained with glass transition temperatures from -52 °C to 61 °C; contact angles in water from 81 ° to 94 °; storage modulus from 108 MPa to 2,756 MPa and loss modulus from 8 MPa to 507 MPa (both in wet state, at 1 Hz frequency and at 37 °C); ultimate tensile strength from 8 MPa to 62 MPa, toughness from 23 MJ/m3 to 287 MJ/m3, strain at break from 3 % to 278 %, macro-scale Young's modulus from 110 MPa to 2,184 MPa (all in wet state); and nano-scale Young's modulus from 6 kPa to 15,019 kPa (in wet state). With respect to in vitro degradation in phosphate buffered saline at 37 °C, some polymeric films [e.g. poly(glycolide-lactide) 30 / 70] started degrading from day 7 (shortest timepoint assessed), whilst others [e.g. poly(glycolide-co-ε-caprolactone) 10 / 90] were more resilient to degradation up to day 21 (longest timepoint assessed). In vitro biological analysis using human dermal fibroblasts and a human monocyte cell line (THP-1) showed the potential of the polymeric films to support cell growth and controlled immune response. Evidently, the selected polymers exhibited properties suitable for a range of clinical indications.This work has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie, grant agreement no. 676338; the Widespread: Twinning, grant agreement no. 810850; and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, grant agreement no. 866126. This work was also supported by Science Foundation Ireland, Career Development Award, grant agreement no. 15/CDA/3629 and Science Foundation Ireland/European Regional Development Fund, grant agreement no. 13/RC/2073. We would also like to thank Darlene Nebinger, Danielle Lord and Oswaldo Fabian from Medtronic North Haven, USA, for all their technical/experimental support

Development of a Connected Sensor System in Colorectal Surgery:User-Centered Design Case Study

BACKGROUND: A successful innovative medical device is not only technically challenging to develop but must also be readily usable to be integrated into health care professionals’ daily practice. Through a user-centered design (UCD) approach, usability can be improved. However, this type of approach is not widely implemented from the early stages of medical device development. OBJECTIVE: The case study presented here shows how UCD may be applied at the very early stage of the design of a disruptive medical device used in a complex hospital environment, while no functional device is available yet. The device under study is a connected sensor system to detect colorectal anastomotic leakage, the most detrimental complication following colorectal surgery, which has a high medical cost. We also aimed to provide usability guidelines for the initial design of other innovative medical devices. METHODS: UCD was implemented by actively involving health care professionals and all the industrial partners of the project. The methodology was conducted in 2 European hospitals: Grenoble-Alpes University Hospital (France) and Erasmus Medical Center Rotterdam (the Netherlands). A total of 6 elective colorectal procedures and 5 ward shifts were observed. In total, 4 workshops were conducted with project partners and clinicians. A formative evaluation was performed based on 5 usability tests using nonfunctional prototype systems. The case study was completed within 12 months. RESULTS: Functional specifications were defined for the various components of the medical device: device weight, size, design, device attachment, and display module. These specifications consider the future integration of the medical device into current clinical practice (for use in an operating room and patient follow-up inside the hospital) and interactions between surgeons, nurses, nurse assistants, and patients. By avoiding irrelevant technical development, this approach helps to promote cost-effective design. CONCLUSIONS: This paper presents the successful deployment over 12 months of a UCD methodology for the design of an innovative medical device during its early development phase. To help in reusing this methodology to design other innovative medical devices, we suggested best practices based on this case

Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

Background: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and Methods: The effect of macrophages cultured on polypropylene (PP) or polyethylene terephthalate coated with a collagen film (PET/Col) on ASCs in monolayer or on the same material was examined either through conditioned medium (CM) or in a direct coculture. ASC proliferation, collagen production, and gene expression were examined. As comparison, the effect of macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFNγ) [M(LPS/IFNγ)] or interleukin (IL) 4 [M(IL-4)] on ASCs was examined. Results: Macrophage-CM increased collagen deposition, proliferation, and gene expression of MMP1, PLOD2, and PTGS2 in ASCs, irrespective of the material. Culturing ASCs and macrophages in coculture when only macrophages were on the materials induced the same effects on gene expression. When both ASCs and macrophages were cultured on biomaterials, PP induced COL1A1 and MMP1 more than PET/Col. M(LPS/IFNγ) CM increased PLOD2, MMP1, and PTGS2 and decreased TGFB in ASCs more than the M(IL-4) CM. Conclusion: Biomaterials influence wound healing by influencing the interaction between macrophages and ASCs. We provided more insight into the behavior of different cell types during wound healing. This behavior appears to be biomaterial specific depending on which cell type interacts with the biomaterial. As such, the biomaterial will influence tissue regeneration

Marine origin collagens and its potential applications

Collagens are the most abundant high molecular weight proteins in both invertebrate and vertebrate organisms, including mammals, and possess mainly a structural role, existing different types according with their specific organization in distinct tissues. From this, they have been elected as one of the key biological materials in tissue regeneration approaches. Also, industry is constantly searching for new natural sources of collagen and upgraded methodologies for their production. The most common sources are from bovine and porcine origin, but other ways are making their route, such as recombinant production, but also extraction from marine organisms like fish. Different organisms have been proposed and explored for collagen extraction, allowing the sustainable production of different types of collagens, with properties depending on the kind of organism (and their natural environment) and extraction methodology. Such variety of collagen properties has been further investigated in different ways to render a wide range of applications. The present review aims to shed some light on the contribution of marine collagens for the scientific and technological development of this sector, stressing the opportunities and challenges that they are and most probably will be facing to assume a role as an alternative source for industrial exploitation.The authors would like to acknowledge the funding from ERDF through Atlantic Area Transnational Cooperation Programme Project 2011-1/164 MARMED, POCTEP Projects 0330_IBEROMARE_1_P and 0687_NOVOMAR_1_P and from European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements nr. KBBE-2010-266033-SPECIAL and nr. REGPOT-CT2012-316331-POLARIS. The Portuguese Foundation for Science and Technology is also acknowledged for the Post-Doc fellowship SFRH/BPD/70230/2010 (JMS)

Monocyte subsets in blood correlate with obesity related response of macrophages to biomaterials in vitro

Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects th

Multi-disciplinary investigation of fluid seepage on an unstable margin: The case of the Central Nile deep sea fan

We report on a multidisciplinary study of cold seeps explored in the Central Nile deep-sea fan of the Egyptian margin. Our approach combines in situ seafloor observation, geophysics, sedimentological data, measurement of bottom-water methane anomalies, pore-water and sediment geochemistry, and 230Th/U dating of authigenic carbonates. Two areas were investigated, which correspond to different sedimentary provinces. The lower slope, at ∼ 2100 m water depth, indicates deformation of sediments by gravitational processes, exhibiting slope-parallel elongated ridges and seafloor depressions. In contrast, the middle slope, at ∼ 1650 m water depth, exhibits a series of debris-flow deposits not remobilized by post-depositional gravity processes. Significant differences exist between fluid-escape structures from the two studied areas. At the lower slope, methane anomalies were detected in bottom-waters above the depressions, whereas the adjacent ridges show a frequent coverage of fractured carbonate pavements associated with chemosynthetic vent communities. Carbonate U/Th age dates (∼ 8 kyr BP), pore-water sulphate and solid phase sediment data suggest that seepage activity at those carbonate ridges has decreased over the recent past. In contrast, large (∼ 1 km2) carbonate-paved areas were discovered in the middle slope, with U/Th isotope evidence for ongoing carbonate precipitation during the Late Holocene (since ∼ 5 kyr BP at least). Our results suggest that fluid venting is closely related to sediment deformation in the Central Nile margin. It is proposed that slope instability leads to focused fluid flow in the lower slope and exposure of ‘fossil’ carbonate ridges, whereas pervasive diffuse flow prevails at the unfailed middle slope

The large-scale evolution of neodymium isotopic composition in the global modern and Holocene ocean revealed from seawater and archive data

Neodymium isotopic compositions (143Nd/144Nd or εNd) have been used as a tracer of water masses and lithogenic inputs to the ocean. To further evaluate the faithfulness of this tracer, we have updated a global seawater εNd database and combined it with hydrography parameters (temperature, salinity, nutrients and oxygen concentrations), carbon isotopic ratio and radiocarbon of dissolved inorganic carbon. Archive εNd data are also compiled for leachates, foraminiferal tests, deep-sea corals and fish teeth/debris from the Holocene period (< 10,000 years). At water depths ≥ 1500 m, property-property plots show clear correlations between seawater εNd and the other variables, suggesting that large-scale water mass mixing is a primary control of deepwater εNd distribution. At ≥ 200 m, basin-scale seawater T-S-εNd diagrams demonstrate the isotopic evolution of different water masses. Seawater and archive εNd values are compared using property-property plots and T-S-εNd diagrams. Archive values generally agree with corresponding seawater values although they tend to be at the upper limit in the Pacific. Both positive and negative offsets exist in the northern North Atlantic. Applying multiple regression analysis to deep (≥ 1500 m) seawater data, we established empirical equations that predict the main, large-scale, deepwater εNd trends from hydrography parameters. Large offsets from the predicted values are interpreted as a sign of significant local/regional influence. Dominant continental influence on seawater and archive εNd is observed mainly within 1000 km from the continents. Generally, seawater and archive εNd values form gradual latitudinal trend in the Atlantic and Pacific at depths ≥ 600 m, consistent with the idea that Nd isotopes help distinguish between northern/southern sourced water contributions at intermediate and deep water depths

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection

Aim: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. Method: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. Results: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0–14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). Conclusion: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool