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To better simulate the clinical scenario, we suggest that treatment should be done in our future studies in a nonunion model instead of an immediate implantation upon the creation of the bone defect.
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Central to acute inflammation are the recruitment and activation of neutrophils), which rapidly localise to the implantation site upon release of chemoattractants by activated platelets [ 52, 53] and endothelial cells [ 54– 54].
Upon subcutaneous implantation, the implanted cells maintained the SMC phenotype.
In addition, ELISPOT analysis demonstrated the induction of IFN-γ-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS.
These results demonstrate that BMSC-Luc and BMSC-Luc/eGFP/Pac specific IFN-γ-producing T-cells are efficiently induced upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating potential immunogenicity of our reporter gene-modified BMSC for the peripheral immune system, but not for the CNS immune system.
However, such conventional tissue engineering approaches suffer from inherent problems of non-homogeneous distribution of cells, failure to integrate and vascularize upon implantation with subsequent rejection of the implanted biomaterial along with formed skin (Verseijden et al. 2010).
A significant enhancement, by at least a factor of two, of implant size was also found upon implantation of embryonic pig liver in Factor VIII KO SCID mice, as evaluated by ELISA for pig blood albumin levels (Fig. 3D).
Upon implantation dose and average beam flux, the retained concentration of Fe implants ranges between 22 at.% and lower than 10 at.%.
The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation.
The translational potential of engineered cartilage relies upon developing tissue capable of withstanding in vivo loads upon implantation and utilizing a clinically relevant cell source, such as costochondral cells.
For example, mice carrying loss of function alleles for TAF10, TAF8, TAF7, or TBP die between blastocyst and pre-implantation stages upon depletion of the maternal protein (Voss et al., 2000; Martianov et al., 2002; Mohan et al., 2003; Gegonne et al., 2012).
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