KR-12 Derivatives Endow Nanocellulose with Antibacterial and Anti-Inflammatory Properties: Role of Conjugation Chemistry.

This work combines the wound-healing-related properties of the host defense peptide KR-12 with wood-derived cellulose nanofibrils (CNFs) to obtain bioactive materials, foreseen as a promising solution to treat chronic wounds. Amine coupling through carbodiimide chemistry, thiol-ene click chemistry, and Cu(I)-catalyzed azide-alkyne cycloaddition were investigated as methods to covalently immobilize KR-12 derivatives onto CNFs. The effects of different coupling chemistries on the bioactivity of the KR12-CNF conjugates were evaluated by assessing their antibacterial activities against Escherichia coli and Staphylococcus aureus. Potential cytotoxic effects and the capacity of the materials to modulate the inflammatory response of lipopolysaccharide (LPS)-stimulated RAW 245.6 macrophages were also investigated. The results show that KR-12 endowed CNFs with antibacterial activity against E. coli and exhibited anti-inflammatory properties and those conjugated by thiol-ene chemistry were the most bioactive. This finding is attributed to a favorable peptide conformation and accessibility (as shown by molecular dynamics simulations), driven by the selective chemistry and length of the linker in the conjugate. The results represent an advancement in the development of CNF-based materials for chronic wound care. This study provides new insights into the effect of the conjugation chemistry on the bioactivity of immobilized host defense peptides, which we believe to be of great value for the use of host defense peptides as therapeutic agents.

A Synthetic Cyclized Antimicrobial Peptide with Potent Effects against Drug-Resistant Skin Pathogens.

Dermal infections requiring treatment are usually treated with conventional antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defense peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant-type strains and clinical isolates of common skin pathogens in the low (<2) µM range. In addition, it influences innate immunity in keratinocytes, and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes. Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic-resistant bacteria.

Biocompatibility of a Zr-Based Metallic Glass Enabled by Additive Manufacturing.

The present work explored the use of the selective laser melting (SLM) technique to develop a Zr-based bulk metallic glass (BMG) and investigate the influence of the process parameters on obtaining different levels of surface roughness. Moreover, the potential of the additively manufactured BMG Zr59.3Cu28.8Al10.4Nb1.5 (trade name AMLOY-ZR01) as an implant material was studied by evaluating the osteoblastic cell response to the alloy and its stability under simulated biological environments. The materials were characterized in terms of degree of crystallinity, surface roughness, and morphology, followed by a systematic investigation of the response of the MC3T3-E1 preosteoblastic cell line to the as-printed samples. The materials supported cell proliferation and differentiation of the preosteoblastic cells, with results comparable to the reference material Ti-6Al-4V. The surface microroughness and surface morphology (porous or groove-type laser tracks) investigated in this study did not have a significant effect on modulating the cell response. Ion release experiments showed a large increase in ion release under inflammatory conditions as compared to regular physiological conditions, which could be attributed to the increased local corrosion under inflammatory conditions. The findings in this work showed that the surface roughness of the additively manufactured BMG AMLOY-ZR01 can be tailored by controlling the laser power applied during the SLM process. The favorable cell response to the as-printed AMLOY-ZR01 represents of a significant advancement of the investigation of additively manufactured BMGs for orthopedic applications, while the results of the ion release study highlights the effect that inflammatory conditions could have on the degradation of the alloy.

A stable cyclized antimicrobial peptide derived from LL-37 with host immunomodulatory effects and activity against uropathogens.

The increasing antibiotic resistance among uropathogenic bacteria warrants alternative therapeutic strategies. We demonstrate the potential of the synthetic peptide CD4-PP, designed by dimerization and backbone cyclization of the shortest antimicrobial region of human cathelicidin, LL-37. CD4-PP is active against clinical and type strains of common uropathogens Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa at concentrations substantially below cellular cytotoxic levels and induced membrane deformation and leakage in E. coli and P. aeruginosa. Furthermore, CD4-PP treatment prevented the formation of new biofilm and dissolved mature biofilm created by E. coli and P. aeruginosa and targeted curli amyloid in E. coli biofilms. In addition, CD4-PP also induced production of LL-37 by uroepithelial cells and increased the expression of tight junction proteins claudin-14 and occludin. During uroepithelial cell infection, CD4-PP significantly reduced uropathogen survival when treatment was given at the start of infection. Low micromolar of CD4-PP treatment initiated after 2 h was successful with all tested species, except P. aeruginosa where CD4-PP was unable to reduce survival, which could be attributed by early biofilm formation. Finally, we demonstrated that urinary catheter pieces coated with saline fluid supplemented with CD4-PP reduced the attachment of E. coli, giving it a potential clinical application.

Validation of the Trackhealth physical activity monitor / Validação do monitor de atividade física Trackhealth

ABSTRACT This is a quantitative methodological study for the validation of a research instrument. It aimed to validate the data from the TrackHealth accelerometry device. The sample consisted of 30 adult individuals of both sexes selected by convenience who met the inclusion and exclusion criteria. The physical activity monitors used for the research protocol were the ActiGraph® wGT3X-BT triaxial accelerometer and the TrackHealth accelerometer (TH). The activity protocol consisted of 4 (four) activities (walking at 4.8 and 6.4 km h1 and running at 9.7 and 12 km h1) performed in the laboratory, on an Ibramed treadmill, lasting 5 (five) minutes at each stage. A difference was found between the raw acceleration data of the two devices, however the TrackHealth device showed higher sensitivity at speeds of 4.8 and 6.4 km/h, and a high level of agreement (2.7-2.8%) at the initial speeds of the magnitude vectors. However, there is still a need for improvement in the functioning of the device, so that TrackHealth can be commercialized.

RESUMO Trata-se de um estudo metodológico quantitativo para validação de um instrumento de pesquisa. O objetivo era validar os dados do dispositivo de acelerometria TrackHealth. A amostra foi composta por 30 indivíduos adultos de ambos os sexos selecionados por conveniência que atenderam aos critérios de inclusão e exclusão. Os monitores de atividade física utilizados para o protocolo de pesquisa foram o acelerômetro triaxial ActiGraph® wGT3X-BT e o acelerômetro TrackHealth (TH). O protocolo de atividades consistiu em 4 (quatro) atividades (caminhada a 4,8 e 6,4 km h1 e corrida a 9,7 e 12 km h1) realizadas em laboratório, em esteira Ibramed, com duração de 5 (cinco) minutos em cada etapa. Foi encontrada uma diferença entre os dados brutos de aceleração dos dois dispositivos, no entanto, o dispositivo TrackHealth apresentou maior sensibilidade nas velocidades de 4,8 e 6,4 km / h, e um alto nível de concordância (2,7-2,8%) nas velocidades iniciais da magnitude vetores. Porém, ainda há necessidade de melhorias no funcionamento do aparelho, para que o TrackHealth possa ser comercializado.

Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose.

Wood-derived nanofibrillated cellulose (NFC) has emerged as a sustainable material with a wide range of applications and increasing presence in the market. Surface charges are introduced during the preparation of NFC to facilitate the defibrillation process, which may also alter the toxicological properties of NFC. In the present study, we examined the in vitro toxicity of NFCs with five surface chemistries: nonfunctionalized, carboxymethylated, phosphorylated, sulfoethylated, and hydroxypropyltrimethylammonium-substituted. The NFC samples were characterized for surface functional group density, surface charge, and fiber morphology. Fibril aggregates predominated in the nonfunctionalized NFC, while individual nanofibrils were observed in the functionalized NFCs. Differences in surface group density among the functionalized NFCs were reflected in the fiber thickness of these samples. In human bronchial epithelial (BEAS-2B) cells, all NFCs showed low cytotoxicity (CellTiter-GloVR luminescent cell viability assay) which never exceeded 10% at any exposure time. None of the NFCs induced genotoxic effects, as evaluated by the alkaline comet assay and the cytokinesis-block micronucleus assay. The nonfunctionalized and carboxymethylated NFCs were able to increase intracellular reactive oxygen species (ROS) formation (chloromethyl derivative of 2',7'-dichlorodihydrofluorescein diacetate assay). However, ROS induction did not result in increased DNA or chromosome damage.

In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator.

There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1-0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.

In Vitro Biological Impact of Nanocellulose Fibers on Human Gut Bacteria and Gastrointestinal Cells.

Wood-derived nanofibrillated cellulose (NFC) has long been recognized as a valuable nanomaterial for food-related applications. However, the safety of NFC cannot be predicted just from the chemical nature of cellulose, and there is a need to establish the effect of the nanofibers on the gastrointestinal tract, to reassure the safe use of NFC in food-related products. The present work selected the intestinal cells Caco-2 and the gut bacteria Escherichia coli and Lactobacillus reuteri to evaluate the in vitro biological response to NFC. NFC materials with different surface modifications (carboxymethylation, hydroxypropyltrimethylammonium substitution, phosphorylation and sulfoethylation) and unmodified NFC were investigated. The materials were characterized in terms of surface functional group content, fiber morphology, zeta potential and degree of crystallinity. The Caco-2 cell response to the materials was evaluated by assessing metabolic activity and cell membrane integrity. The effects of the NFC materials on the model bacteria were evaluated by measuring bacterial growth (optical density at 600 nm) and by determining colony forming units counts after NFC exposure. Results showed no sign of cytotoxicity in Caco-2 cells exposed to the NFC materials, and NFC surface functionalization did not impact the cell response. Interestingly, a bacteriostatic effect on E. coli was observed while the materials did not affect the growth of L. reuteri. The present findings are foreseen to contribute to increase the knowledge about the potential oral toxicity of NFC and, in turn, add to the development of safe NFC-based food products.

Highly Porous Amorphous Calcium Phosphate for Drug Delivery and Bio-Medical Applications.

Amorphous calcium phosphate (ACP) has shown significant effects on the biomineralization and promising applications in bio-medicine. However, the limited stability and porosity of ACP material restrict its practical applications. A storage stable highly porous ACP with Brunauer-Emmett-Teller surface area of over 400 m2/g was synthesized by introducing phosphoric acid to a methanol suspension containing amorphous calcium carbonate nanoparticles. Electron microscopy revealed that the porous ACP was constructed with aggregated ACP nanoparticles with dimensions of several nanometers. Large angle X-ray scattering revealed a short-range atomic order of <20 Å in the ACP nanoparticles. The synthesized ACP demonstrated long-term stability and did not crystallize even after storage for over 14 months in air. The stability of the ACP in water and an α-MEM cell culture medium were also examined. The stability of ACP could be tuned by adjusting its chemical composition. The ACP synthesized in this work was cytocompatible and acted as drug carriers for the bisphosphonate drug alendronate (AL) in vitro. AL-loaded ACP released ~25% of the loaded AL in the first 22 days. These properties make ACP a promising candidate material for potential application in biomedical fields such as drug delivery and bone healing.

Biocompatibility of Nanocellulose-Reinforced PVA Hydrogel with Human Corneal Epithelial Cells for Ophthalmic Applications.

Transparent composite hydrogel in the form of a contact lens made from poly(vinyl alcohol) (PVA) and cellulose nanocrystals (CNCs) was subjected to in vitro biocompatibility evaluation with human corneal epithelial cells (HCE-2 cells). The cell response to direct contact with the hydrogels was investigated by placing the samples on top of confluent cell layers and evaluating cell viability, morphology, and cell layer integrity subsequent to 24 h culture and removal of the hydrogels. To further characterize the lens-cell interactions, HCE-2 cells were seeded on the hydrogels, with and without simulated tear fluid (STF) pre-conditioning, and cell viability and morphology were evaluated. Furthermore, protein adsorption on the hydrogel surface was investigated by incubating the materials with STF, followed by protein elution and quantification. The hydrogel material was found to have affinity towards protein adsorption, most probably due to the interactions between the positively charged lysozyme and the negatively charged CNCs embedded in the PVA matrix. The direct contact experiment demonstrated that the physical presence of the lenses did not affect corneal epithelial cell monolayers in terms of integrity nor cell metabolic activity. Moreover, it was found that viable corneal cells adhered to the hydrogel, showing the typical morphology of epithelial cells and that such response was not influenced by the STF pre-conditioning of the hydrogel surface. The results of the study confirm that PVA-CNC hydrogel is a promising ophthalmic biomaterial, motivating future in vitro and in vivo biocompatibility studies.

Exploring the Use of Amine Modified Mesoporous Magnesium Carbonate for the Delivery of Salicylic Acid in Topical Formulations: In Vitro Cytotoxicity and Drug Release Studies.

Salicylic acid (SA) has for a long time been used to treat various skin disorders due to its anti-inflammatory, bacteriostatic, and antifungal properties. In the present work, mesoporous magnesium carbonate (MMC), a promising drug carrier, was modified with 3-aminopropyl-triethoxysilane to enable loading of SA. The amine modified MMC (aMMC) was successfully loaded with 8 wt.% of SA via a solvent evaporation method. SA was later completely released from the carrier in less than 15 min. Furthermore, the cytotoxicity of the functionalized material was evaluated. aMMC was found to be non-toxic for human dermal fibroblast cells with particle concentration of up to 1000 µg/mL when exposed for 48 h. The presented results form the basis of future development of aMMC as a potential carrier for SA in dermatological applications.

Sedentary behavior among university students: a systematic review / Comportamento sedentário em universitários: uma revisão sistemática

Abstract Estudos sobre o tema do comportamento sedentário (SB) em universitários têm sido publicados, diante disso o conhecimento sobre os métodos adotados torna-se importante para a ciência, e a caracterização das prevalências e fatores associados a esse atributo são essenciais no âmbito das políticas de saúde para esse grupo. Assim, o objetivo do presente estudo foi descrever as prevalências e os fatores associados, e as características metodológicas empregadas nas pesquisas sobre o SB em universitários. Uma busca nas bases de dados National Library of Medicine (PUBMED), Scientific Electronic Library Online (SciELO), Biblioteca Virtual em Saúde (BVS) e SCOPUS foi realizada. Este estudo adotou os itens e recomendações do Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), e os artigos selecionados foram analisados conforme as características metodológicas, além das prevalências e os fatores associados ao SB. Dos 1.740 artigos encontrados nas bases de dados, 23 fizeram parte dessa revisão. Foram observadas prevalências para o tempo sentado de 34,0% a 90,2%. O uso de definições operacionais e pontos de corte foram diversificados, além do uso de variados instrumentos para estimar o SB. Foi observada a falta de padronização entre os pontos de corte para determinação do SB e das definições operacionais, como uso de instrumentos não validados. Dentre os fatores associados com maiores prevalências, destacaram-se o excesso de peso e os sintomas depressivos. Conclui-se que as prevalências de SB foram elevadas em domínios não relacionados ao tempo dedicado aos estudos e características biológicas e psicológicas representaram atributos mais associados ao SB.

Resumo Estudos sobre o tema do comportamento sedentário (SB) em universitários têm sido publicados, diante disso o conhecimento sobre os métodos adotados torna-se importante para a ciência, e a caracterização das prevalências e fatores associados a esse atributo são essenciais no âmbito das políticas de saúde para esse grupo. Assim, o objetivo do presente estudo foi descrever as prevalências e os fatores associados, e as características metodológicas empregadas nas pesquisas sobre o SB em universitários. Uma busca nas bases de dados National Library of Medicine (PUBMED), Scientific Electronic Library Online (SciELO), Biblioteca Virtual em Saúde (BVS) e SCOPUS foi realizada. Este estudo adotou os itens e recomendações do Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), e os artigos selecionados foram analisados conforme as características metodológicas, além das prevalências e os fatores associados ao SB. Dos 1.740 artigos encontrados nas bases de dados, 23 fizeram parte dessa revisão. Foram observadas prevalências para o tempo sentado de 34,0% a 90,2%. O uso de definições operacionais e pontos de corte foram diversificados, além do uso de variados instrumentos para estimar o SB. Foi observada a falta de padronização entre os pontos de corte para determinação do SB e das definições operacionais, como uso de instrumentos não validados. Dentre os fatores associados com maiores prevalências, destacaram-se o excesso de peso e os sintomas depressivos. Conclui-se que as prevalências de SB foram elevadas em domínios não relacionados ao tempo dedicado aos estudos e características biológicas e psicológicas representaram atributos mais associados ao SB.

Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions.

A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.

Development of a systematic method to assess similarity between nanomaterials for human hazard evaluation purposes - lessons learnt.

Within the EU FP-7 GUIDEnano project, a methodology was developed to systematically quantify the similarity between a nanomaterial (NM) that has been tested in toxicity studies and the NM for which risk needs to be evaluated, for the purpose of extrapolating toxicity data between the two materials. The methodology is a first attempt to use current knowledge on NM property-hazard relationships to develop a series of pragmatic and systematic rules for assessing NM similarity. Moreover, the methodology takes into account the practical feasibility, in that it is based on generally available NM characterization information. In addition to presenting this methodology, the lessons learnt and the challenges faced during its development are reported here. We conclude that there is a large gap between the information that is ideally needed and its application to real cases. The current database on property-hazard relationships is still very limited, which hinders the agreement on the key NM properties constituting the basis of the similarity assessment and the development of associated science-based and unequivocal rules. Currently, one of the most challenging NM properties to systematically assess in terms of similarity between two NMs is surface coating and functionalization, which lacks standardized parameters for description and characterization methodology. Standardization of characterization methods that lead to quantitative, unambiguous, and measurable parameters describing NM properties are necessary in order to build a sufficiently robust property-hazard database that allows for evidence-based refinement of our methodology, or any other attempt to systematically assess the similarity of NMs.

Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads.

Sulfonated cellulose beads were prepared by oxidation of Cladophora nanocellulose to 2,3-dialdehyde cellulose followed by sulfonation using bisulfite. The physicochemical properties of the sulfonated beads, i.e., high surface area, high degree of oxidation, spherical shape, and the possibility of tailoring the porosity, make them interesting candidates for the development of immunosorbent platforms, including their application in extracorporeal blood treatments. A desired property for materials used in such applications is blood compatibility; therefore in the present work, we investigate the hemocompatibility of the sulfonated cellulose beads using an in vitro whole blood model. Complement system activation (C3a and sC5b-9 levels), coagulation activation (thrombin-antithrombin (TAT) levels) and hemolysis were evaluated after whole blood contact with the sulfonated beads and the results were compared with the values obtained with the unmodified Cladophora nanocellulose. Results showed that neither of the cellulosic materials presented hemolytic activity. A marked decrease in TAT levels was observed after blood contact with the sulfonated beads, compared with Cladophora nanocellulose. However, the chemical modification did not promote an improvement in Cladophora nanocellulose hemocompatibility in terms of complement system activation. Even though the sulfonated beads presented a significant reduction in pro-coagulant activity compared with the unmodified material, further modification strategies need to be investigated to control the complement activation by the cellulosic materials.

In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels.

Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca2+-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca2+-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca2+-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.

Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties: Candidate materials for advanced wound care applications.

Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.

Hemocompatibility of Ca2+ -Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis.

The present work investigates Ca2+ -crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing-the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.

On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions: Physicochemical properties and application-oriented biocompatibility studies.

Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented biocompatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the material´s potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon direct contact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.

In vitro biological responses to nanofibrillated cellulose by human dermal, lung and immune cells: surface chemistry aspect.

BACKGROUND: Nanocellulose, 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. RESULTS: The 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-ß levels, an effect that was absent when surface charged groups were introduced into NFC. CONCLUSIONS: Taken 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.