BackgroundNanocellulose, and particularly nanofibrillated cellulose (NFC), has been proposed for a diversity of applications in industry and in the biomedical field. Its unique physicochemical and structural features distinguish nanocellulose from traditional materials and enable its use as an advance nanomaterial. However, its nanoscale features may induce unknown biological responses. Limited studies with NFC are available and the biological impacts of its use have not been thoroughly explored. This study assesses the in vitro biological responses elicited by wood-derived NFC gels, when human dermal fibroblasts, lung MRC-5 cells and THP-1 macrophage cells are exposed to the nanomaterial. Furthermore, whether the presence of surface charged groups (i.e. carboxymethyl and hydroxypropyltrimethylammonium groups) on NFC can induce distinct biological responses is investigated.ResultsThe introduction of surface charged groups resulted in individual nanofibrils, while fibril aggregates predominated in the unmodified NFC gel suspensions as observed by transmission electron microscopy. In the presence of proteins, the surface modified NFCs formed compact agglomerates while the agglomeration pattern of the unmodified NFC was similar in the presence of proteins and in physiological buffer. Unmodified and modified NFC gels did not induce cytotoxicity in human dermal fibroblasts, lung and macrophage cells. No significant ROS production by THP-1 macrophages was found and no cellular uptake was observed. However, an inflammatory response was detected when THP-1 macrophages were treated with unmodified NFC as assessed by an increase in TNF-α and IL1-β levels, an effect that was absent when surface charged groups were introduced into NFC.ConclusionsTaken together, the data presented here show the absence of cytotoxic effects associated with the exposure to unmodified, carboxymethylated and hydroxypropyltrimethylammonium-modified NFCs. Unmodified NFC presented a pro-inflammatory effect which can be further moderated by introducing surface modifications such as carboxymethyl and hydroxypropyltrimethylammonium groups into the nanofibrils. The present findings suggest that the inflammatory response to NFC might be driven by the material surface chemistry, and thus open up for the possibility of designing safe nanocellulose materials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0182-0) contains supplementary material, which is available to authorized users.

From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers’ performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013–2016. A second phase was delivered in July 2021 covering 2015–2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this ‘work in progress’, as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.