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Fabrication of composite scaffolds using stereolithography (SLA) for bone tissue engineering has shown great promises. However, in order to trigger effective bone formation and ...implant integration, exogenous growth factors are commonly combined to scaffold materials. In this study, we fabricated biodegradable composite scaffolds using SLA and endowed them with osteopromotive properties in the absence of biologics. First we prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture. Then, we conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in vitro and kinetic of bone healing in vivo. We observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20wt% of HA, along with difference in terms of osteogenesis and degree of implant osseointegration. Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds. To summarize, this work is of substantial importance as it shows how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in vitro and in vivo osteogenesis.
This study reports for the first time the enhance osteopromotion of composite biomaterials, with controlled macro-architecture and microscale distribution of hydroxyapatite particles, manufactured by stereolithography. In this process, the hydroxyapatite particles are not only embedded into an erodible polymer matrix, as reported so far in the literature, but concentrated at the surface of the structures. This leads to robust in vivo bone formation at low concentration of hydroxyapatite. The reported 3D self-corralling composite architecture provides significant opportunities to develop functional biomaterials for bone repair and tissue engineering.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD ...include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent
,
and pre-clinical studies.
To evaluate 1) the relationship between the knee contact force (KCF) and knee adduction and flexion moments (KAM and KFM) during normal gait in people with medial knee osteoarthritis (KOA), 2) the ...effects on the KCF of walking with a modified gait pattern and 3) the relationship between changes in the KCF and changes in the knee moments.
We modeled the gait biomechanics of thirty-five patients with medial KOA using the AnyBody Modeling System during normal gait and two modified gait patterns. We calculated the internal KCF and evaluated the external joint moments (KAM and KFM) against it using linear regression analyses.
First peak medial KCF was associated with first peak KAM (R2 = 0.60) and with KAM and KFM (R2 = 0.73). Walking with both modified gait patterns reduced KAM (P = 0.002) and the medial to total KCF ratio (P < 0.001) at the first peak. Changes in KAM during modified gait were moderately associated with changes in the medial KCF at the first peak (R2 = 0.54 and 0.53).
At the first peak, KAM is a reasonable substitute for the medial contact force, but not at the second peak. First peak KFM is also a significant contributor to the medial KCF. At the first peak, walking with a modified gait reduced the ratio of the medial to total KCF but not the medial KCF itself. To determine the effects of gait modifications on cartilage loading and disease progression, longitudinal studies and individualized modeling, accounting for motion control, would be required.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bone healing complications such as delayed healing or non-union affect 5-10 % of patients with a long-bone fracture and lead to reduced quality of life and increased health-care costs. The gut ...microbiota and the metabolites they produce, mainly short-chain fatty acids (SCFAs), have been shown to impact nearly all organs of the human body including bone. SCFAs show broad activity in positively influencing bone healing outcomes either by acting directly on cell types involved in fracture healing, such as osteoblasts, osteoclasts, chondrocytes and fibroblasts, or indirectly, by shaping an appropriate anti-inflammatory and immune regulatory response. Due to the ability of SCFAs to influence osteoblast and osteoclast differentiation, SCFAs may also affect the integration of orthopaedic implants in bone. In addition, SCFA-derivatives have already been used in a variety of tissue engineering constructs to reduce inflammation and induce bone tissue production. The present review summarises the current knowledge on the role of the gut microbiota, in particular through the action of SCFAs, in the individual stages of bone healing and provides insights into how SCFAs may be utilised in a manner beneficial for fracture healing and surgical reconstruction.
Fracture-related infection (FRI) remains a challenging complication that creates a heavy burden for orthopaedic trauma patients, their families and treating physicians, as well as for healthcare ...systems. Standardization of the diagnosis of FRI has been poor, which made the undertaking and comparison of studies difficult. Recently, a consensus definition based on diagnostic criteria for FRI was published. As a well-established diagnosis is the first step in the treatment process of FRI, such a definition should not only improve the quality of published reports but also daily clinical practice. The FRI consensus group recently developed guidelines to standardize treatment pathways and outcome measures. At the center of these recommendations was the implementation of a multidisciplinary team (MDT) approach. If such a team is not available, it is recommended to refer complex cases to specialized centers where a MDT is available and physicians are experienced with the treatment of FRI. This should lead to appropriate use of antimicrobials and standardization of surgical strategies. Furthermore, an MDT could play an important role in host optimization. Overall two main surgical concepts are considered, based on the fact that fracture fixation devices primarily target fracture consolidation and can be removed after healing, in contrast to periprosthetic joint infection were the implant is permanent. The first concept consists of implant retention and the second consists of implant removal (healed fracture) or implant exchange (unhealed fracture). In both cases, deep tissue sampling for microbiological examination is mandatory. Key aspects of the surgical management of FRI are a thorough debridement, irrigation with normal saline, fracture stability, dead space management and adequate soft tissue coverage. The use of local antimicrobials needs to be strongly considered. In case of FRI, empiric broad-spectrum antibiotic therapy should be started after tissue sampling. Thereafter, this needs to be adapted according to culture results as soon as possible. Finally, a minimum follow-up of 12 months after cessation of therapy is recommended. Standardized patient outcome measures purely focusing on FRI are currently not available but the patient-reported outcomes measurement information system (PROMIS) seems to be the preferred tool to assess the patients’ short and long-term outcome. This review summarizes the current general principles which should be considered during the whole treatment process of patients with FRI based on recommendations from the FRI Consensus Group.
Level of evidence:
Level V.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The grain yield of cereals has almost doubled this century as a result of genetic manipulation by plant breeding. Surprisingly, there has been no change in the rate of photosynthesis per unit leaf ...area to accompany these increases. However, total photosynthesis has increased as a result of an increase in leaf area, daily duration of photosynthesis or leaf area duration. There remain substantial opportunities to continue to improve total photosynthesis and crop yield genetically using conventional breeding practices. Selectable traits are discussed here in the context of increasing total above‐ground biomass under favourable conditions. Opportunities exist to alter crop duration and the timing of crop development to match it better to radiation, temperature and vapour pressure during crop growth, and to increase the rate of development of early leaf area to achieve rapid canopy closure. The importance of these traits will depend on the environment in which the crop is grown. Increases in crop photosynthesis through breeding are also likely to come via indirect means. Selection for a high and sustained stomatal conductance during the period of stem elongation is one way. Increasing assimilate allocation to the reproductive primordia so as to establish a large potential sink should also indirectly increase total crop photosynthesis. Evidence in the major grain crops suggests that by anthesis the capacity for photosynthesis is high and that photosynthesis is not limiting during grain filling. To use this surplus capacity it is suggested that carbon and nitrogen partitioning to the reproductive meristem be increased so as to establish a high potential grain number and the potential for a large grain size. It is then expected that additional photosynthesis will follow, either by a longer daily duration of photosynthesis or by an extended leaf area duration.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
is a permanent member of the normal human microbiota, commonly found on skin and mucous membranes. By adhering to tissue surface moieties of the host via specific adhesins,
is capable of establishing ...a lifelong commensal relationship with humans that begins early in life. In its role as a commensal organism,
is thought to provide benefits to human host, including out-competing more virulent pathogens. However, largely due to its capacity to form biofilm on implanted foreign bodies,
has emerged as an important opportunistic pathogen in patients receiving medical devices.
causes approximately 20% of all orthopedic device-related infections (ODRIs), increasing up to 50% in late-developing infections. Despite this prevalence, it remains underrepresented in the scientific literature, in particular lagging behind the study of the
. This review aims to provide an overview of the interactions of
with the human host, both as a commensal and as a pathogen. The mechanisms retained by
that enable colonization of human skin as well as invasive infection, will be described, with a particular focus upon biofilm formation. The host immune responses to these infections are also described, including how
seems to trigger low levels of pro-inflammatory cytokines and high levels of interleukin-10, which may contribute to the sub-acute and persistent nature often associated with these infections. The adaptive immune response to
remains poorly described, and represents an area which may provide significant new discoveries in the coming years.
The effective reproduction number Rt is an epidemiological quantity that provides an instantaneous measure of transmission potential of an infectious disease. While dengue is an increasingly ...important vector-borne disease, few have used Rt as a measure to inform public health operations and policy for dengue. This study demonstrates the utility of Rt for real time dengue surveillance. Using nationally representative, geo-located dengue case data from Singapore over 2010-2020, we estimated Rt by modifying methods from Bayesian (EpiEstim) and filtering (EpiFilter) approaches, at both the national and local levels. We conducted model assessment of Rt from each proposed method and determined exogenous temporal and spatial drivers for Rt in relation to a wide range of environmental and anthropogenic factors. At the national level, both methods achieved satisfactory model performance (R2EpiEstim = 0.95, R2EpiFilter = 0.97), but disparities in performance were large at finer spatial scales when case counts are low (MASE EpiEstim = 1.23, MASEEpiFilter = 0.59). Impervious surfaces and vegetation with structure dominated by human management (without tree canopy) were positively associated with increased transmission intensity. Vegetation with structure dominated by human management (with tree canopy), on the other hand, was associated with lower dengue transmission intensity. We showed that dengue outbreaks were preceded by sustained periods of high transmissibility, demonstrating the potential of Rt as a dengue surveillance tool for detecting large rises in dengue cases. Real time estimation of Rt at the fine scale can assist public health agencies in identifying high transmission risk areas and facilitating localised outbreak preparedness and response.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cyanobacterial blooms in western Lake Erie have recently garnered widespread attention. Current evidence indicates that a major source of the nutrients that fuel these blooms is the Maumee River. We ...applied a seasonal trend decomposition technique to examine long-term and seasonal changes in Maumee River discharge and nutrient concentrations and loads. Our results indicate similar long-term increases in both regional precipitation and Maumee River discharge (1975–2013), although changes in the seasonal cycles are less pronounced. Total and dissolved phosphorus concentrations declined from the 1970s into the 1990s; since then, total phosphorus concentrations have been relatively stable, while dissolved phosphorus concentrations have increased. However, both total and dissolved phosphorus loads have increased since the 1990s because of the Maumee River discharge increases. Total nitrogen and nitrate concentrations and loads exhibited patterns that were almost the reverse of those of phosphorus, with increases into the 1990s and decreases since then. Seasonal changes in concentrations and loads were also apparent with increases since approximately 1990 in March phosphorus concentrations and loads. These documented changes in phosphorus, nitrogen, and suspended solids likely reflect changing land-use practices. Knowledge of these patterns should facilitate efforts to better manage ongoing eutrophication problems in western Lake Erie.
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IJS, KILJ, NUK, PNG, UL, UM
Wheat yields globally will depend increasingly on good management to conserve rainfall and new varieties that use water efficiently for grain production. Here we propose an approach for developing ...new varieties to make better use of deep stored water. We focus on water-limited wheat production in the summer-dominant rainfall regions of India and Australia, but the approach is generally applicable to other environments and root-based constraints. Use of stored deep water is valuable because it is more predictable than variable in-season rainfall and can be measured prior to sowing. Further, this moisture is converted into grain with twice the efficiently of in-season rainfall since it is taken up later in crop growth during the grain-filling period when the roots reach deeper layers. We propose that wheat varieties with a deeper root system, a redistribution of branch root density from the surface to depth, and with greater radial hydraulic conductivity at depth would have higher yields in rainfed systems where crops rely on deep water for grain fill. Developing selection systems for mature root system traits is challenging as there are limited high-throughput phenotyping methods for roots in the field, and there is a risk that traits selected in the lab on young plants will not translate into mature root system traits in the field. We give an example of a breeding programme that combines laboratory and field phenotyping with proof of concept evaluation of the trait at the beginning of the selection programme. This would greatly enhance confidence in a high-throughput laboratory or field screen, and avoid investment in screens without yield value. This approach requires careful selection of field sites and years that allow expression of deep roots and increased yield. It also requires careful selection and crossing of germplasm to allow comparison of root expression among genotypes that are similar for other traits, especially flowering time and disease and toxicity resistances. Such a programme with field and laboratory evaluation at the outset will speed up delivery of varieties with improved root systems for higher yield.
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