ObjectivesThis systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.MethodsA systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group.ResultsA total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies.ConclusionsThis review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element.Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1.

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forest ecosystems sequester large amounts of atmospheric co 2 , and the contribution from seasonally dry tropical forests is not negligible. thus, the objective of this study was to quantify and evaluate the seasonal and annual patterns of co 2 exchanges in the Caatinga biome, as well as to evaluate the ecosystem condition as carbon sink or source during years. in addition, we analyzed the climatic factors that control the seasonal variability of gross primary production (Gpp), ecosystem respiration (R eco) and net ecosystem co 2 exchange (nee). Results showed that the dynamics of the components of the co 2 fluxes varied depending on the magnitude and distribution of rainfall and, as a consequence, on the variability of the vegetation state. Annual cumulative NEE was significantly higher (p < 0.01) in 2014 (−169.0 g C m −2) when compared to 2015 (−145.0 g C m −2) and annual NEP/GPP ratio was 0.41 in 2014 and 0.43 in 2015. Global radiation, air and soil temperature were the main factors associated with the diurnal variability of carbon fluxes. Even during the dry season, the NEE was at equilibrium and the Caatinga acted as an atmospheric carbon sink during the years 2014 and 2015. CO 2 concentration has a high interannual variability due to its absorption by terrestrial ecosystems (carbon sinks) 1-5. However, despite this variability, data show a systematic increase in CO 2 throughout the years 6,7. In South America, the Amazon forest is an example of a terrestrial carbon sink (considering its 20-year mean behavior), although it has occasionally behaved as CO 2-neutral or even a carbon source in the last years 8. Interannual variability and trends in CO 2 sinks are controlled by different biogeographic regions. The annual mean behavior of sinks is controlled mainly by highly productive lands, such as wet tropical forests (i.e. the Amazon forest) 5. On the other hand, semiarid environments control the global scale trends observed in the last few decades 9,10. Despite its prominent role, there is still much to be studied and investigated regarding CO 2 exchanges in these regions, which are still much less understood than wet forests or croplands 5,10. According to the literature 10 , gaps in understanding CO 2 exchanges in these environments have limited our ability to understand and predict interannual and decadal variations on global scale carbon cycle. There are a few inherent difficulties when quantifying CO 2 exchanges in semiarid environments, such as the rapid expansion of some of its areas due to climate change and anthropic activities 11,12. Studies show that some regions in South America are becoming more arid, such as the Amazon 13,14 ; the Brazilian semiarid region, dominated by the Caatinga biome, which is a seasonally dry tropical forest (SDTF) 15-17 and the Cerrado, which is a Brazilian savanna-type vegetation 18 .

BackgroundAseptic loosening (AL) of hip prosthesis presents inflammation and pain as sign and symptom similarly to arthritis pathologies. Still, the immune and innervation profiles in hip AL remain unclear and their interplay is poorly explored. Herein, local tissue inflammatory response, sensory and sympathetic innervation as well as associated local mediators were assessed in hip joint microenvironment underlying AL and compared to osteoarthritis (OA).MethodsHistopathological analysis, immune cells (macrophages, T, B cells and PMNs) as well as sensory and sympathetic nerve fibers (SP+, CGRP+, TH+) distribution and profiles were analyzed on tissues retrieved from patients with failed hip prostheses due to AL (n = 20) and hip OA (n = 15) by immunohistochemistry. Additionally, transcriptional levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12a, iNOS), anti-inflammatory cytokine (IL-10), osteoclastic factor (RANKL) and bone remodeling factor (TGF-β1) were locally evaluated by qRT-PCR. Serum TGF-β1 levels were assessed preoperatively by ELISA.ResultsHistopathological analysis revealed that tissues, aseptic interface membranes of AL patients had distinct tissue architecture and immune cells profile when compared to OA synovial tissues. Macrophages, T cells and B cells showed significant differences in tissue distribution. In OA, inflammation is mostly confined to the vicinity of synovial membrane while in AL macrophages infiltrated throughout the tissue. This differential immune profile is also accompanied with a distinct pattern of sensory and sympathetic innervation. Importantly, in AL patients, a lack of sympathetic innervation aseptic interface membranes without compensation mechanisms at cellular levels was observed with simultaneous reorganization of sensorial innervation. Despite the different histopathological portrait, AL and OA patients exhibited similar transcriptional levels of genes encoding key proteins in local immune response. Nevertheless, in both pathologies, TGF-β1 expression was prominent in sites where the inflammation is occurring. However, at systemic level no differences were found.ConclusionThese findings indicate that AL patients exhibit different local inflammatory response and innervation signatures from OA patients in hip joint. These insights shed the light on neuro-immune interplay in AL and highlight the need to better understand this crosstalk to unravel potential mechanisms for targeted-therapies to improve hip joint lifetime and treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0950-5) contains supplementary material, which is available to authorized users.