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QC 20240313

Histoplasmosis is a respiratory disease caused by Histoplasma capsulatum, a dimorphic fungus, with high mortality and morbidity rates, especially in immunocompromised patients. Considering the small existing therapeutic arsenal, new treatment approaches are still required. Chitosan, a linear polysaccharide obtained from partial chitin deacetylation, has anti-inflammatory, antimicrobial, biocompatibility, biodegradability, and non-toxicity properties. Chitosan with different deacetylation degrees and molecular weights has been explored as a potential agent against fungal pathogens. In this study, the chitosan antifungal activity against H. capsulatum was evaluated using the broth microdilution assay, obtaining minimum inhibitory concentrations (MIC) ranging from 32 to 128 µg/mL in the filamentous phase and 8 to 64 µg/mL in the yeast phase. Chitosan combined with classical antifungal drugs showed a synergic effect, reducing chitosan’s MICs by 32 times, demonstrating that there were no antagonistic interactions relating to any of the strains tested. A synergism between chitosan and amphotericin B or itraconazole was detected in the yeast-like form for all strains tested. For H. capsulatum biofilms, chitosan reduced biomass and metabolic activity by about 40% at 512 µg/mL. In conclusion, studying chitosan as a therapeutic strategy against Histoplasma capsulatum is promising, mainly considering its numerous possible applications, including its combination with other compounds., QC 20240115

Biomaterials made of self-assembling protein building blocks are widely explored for biomedical applications, for example, as drug carriers, tissue engineering scaffolds, and functionalized coatings. It has previously been shown that a recombinant spider silk protein functionalized with a cell binding motif from fibronectin, FN-4RepCT (FN-silk), self-assembles into fibrillar structures at interfaces, i.e., membranes, fibers, or foams at liquid/air interfaces, and fibrillar coatings at liquid/solid interfaces. Recently, we observed that FN-silk also assembles into microspheres in the bulk of a physiological buffer (PBS) solution. Herein, we investigate the self-assembly process of FN-silk into microspheres in the bulk and how its progression is affected by the presence of hyaluronic acid (HA), both in solution and in a cross-linked HA hydrogel. Moreover, we characterize the size, morphology, mesostructure, and protein secondary structure of the FN-silk microspheres prepared in PBS and HA. Finally, we examine how the FN-silk microspheres can be used to mediate cell adhesion and spreading of human mesenchymal stem cells (hMSCs) during cell culture. These investigations contribute to our fundamental understanding of the self-assembly of silk protein into materials and demonstrate the use of silk microspheres as additives for cell culture applications., QC 20240703

Close to half of the world's pregnancies are still unplanned, reflecting a clear unmet need in contraception. Ideally, a contraceptive would provide the high efficacy of hormonal treatments, without systemic side effects. Here, we studied topical reinforcement of the cervical mucus by chitosan mucoadhesive polymers as a form of female contraceptive. Chitosans larger than 7 kDa effectively cross-linked human ovulatory cervical mucus to prevent sperm penetration in vitro. We then demonstrated in vivo using the ewe as a model that vaginal gels containing chitosan could stop ram sperm at the entrance of the cervical canal and prevent them from reaching the uterus, whereas the same gels without chitosan did not substantially limit sperm migration. Chitosan did not affect sperm motility in vitro or in vivo, suggesting reinforcement of the mucus physical barrier as the primary mechanism of action. The chitosan formulations did not damage or irritate the ewe vaginal epithelium, in contrast to nonoxynol-9 spermicide. The demonstration that cervical mucus can be reinforced topically to create an effective barrier to sperm may therefore form the technological basis for mucocervical barrier contraceptives with the potential to become an alternative to hormonal contraceptives., QC 20230307

Mucus is a self-healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel’s mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%–5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature’s example, bovine submaxillary mucins (BSMs) are assembled into “mucus-like” gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self-healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV-1) and genital herpes virus type 2 (HSV-2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV-1 significantly less and do not inhibit HSV-2. Mechanistically, the prophylaxis of HIV-1 infection by BSM gels is found to be that the gels trap HIV-1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission., QC 20221216

Hydrogel biomaterials have found use in various biomedical applications partly due to their biocompatibility and tuneable viscoelastic properties. The ideal rheological properties of hydrogels depend highly on the application and should be considered early in the design process. Rheometry is the most common method to study the viscoelastic properties of hydrogels. However, rheometers occupy much space and are costly instruments. On the other hand, quartz crystal resonators (QCRs) are devices that can be used as low-cost, small, and accurate sensors to measure the viscoelastic properties of fluids. For this reason, we explore the capabilities of a low-cost and compact QCR sensor to sense and characterise the gelation process of hydrogels while using a low sample amount and by sensing two different crosslink reactions: covalent bonds and divalent ions. The gelation of covalently crosslinked mucin hydrogels and physically crosslinked alginate hydrogels could be monitored using the sensor, clearly distinguishing the effect of several parameters affecting the viscoelastic properties of hydrogels, including crosslinking chemistry, polymer concentrations, and crosslinker concentrations. QCR sensors offer an economical and portable alternative method to characterise changes in a hydrogel material's viscous properties to contribute to this type of material design, thus providing a novel approach., QC 20221206

The importance of lubrication between oral surfaces provided by the salivary film is most acutely apparent when it is disrupted, a prevalent consequence of salivary gland hypofunction experienced with aging, a symptom of certain diseases, or a side effect of some medical interventions. Sufferers report difficulty with speech and oral food processing and collectively is detrimental to quality of life. Polyethylene glycol (PEG) is widely employed as a successful biocompatible boundary lubricant in engineering and biomedical applications. It is hypothesized that the immobilization of PEG to biological materials such as oral epithelial cells and tissue can mimic the salivary film and provide durable relief from the symptoms of mucosal dryness. To do so, PEG is functionalized with a sugar binding lectin (wheat germ agglutinin) to enhance epithelial adhesion through lectin-sugar interactions. Retention and lubricity are characterized on an ex vivo oral tissue tribology rig. WGA-PEG coats and retains on mucin films, oral epithelial cells, and porcine tongue tissue, and offers sustained reduction in coefficient of friction (COF). WGA-PEG could be developed into a useful topical treatment for reducing oral friction and the perception of dry mouth., QC 20220615

Biocatalytical upgrading of side streams from agricultural biomass into multifunctional materials constitutes a very attractive option to increase the circularity of food and material systems. We propose the design of radical scavenging hydrogels with mechanical integrity and protective effects against reactive oxygen species by enzymatic crosslinking of arabinoxylans (AX) with high ferulic acid content extracted from corn fibre using subcritical water. We have compared the influence of two enzymatic systems, laccase/O2 and peroxidase/H2O2, on the biochemical structure, multiscale assembly, physicochemical properties, and radical scavenging activity of the polysaccharide hydrogels. Peroxidase crosslinking results in instant hydrogel formation, whereas laccase shows slower crosslinking kinetics, resulting in a more elastic gel network. Characterization by size exclusion chromatography, small angle X-ray scattering, and microscopy revealed structural differences in the network organization of the hydrogels produced by the two enzymes. Laccase crosslinking leads to smaller polymeric aggregates, promoting their progressive organization in network clusters that impact the overall ultrastructure. Conversely, the fast crosslinking induced by peroxidase results in higher porosity and forms larger and potentially more heterogeneous aggregates, which seem to hinder their subsequent association in clusters. Both AX hydrogels exhibit adequate biocompatibility and protective effects against in vitro cellular oxidative stress compared to an alginate reference. This constitutes a proof of concept of the potential application of radical scavenging hydrogels from agricultural side streams for biomedical and nutritional applications in wound healing, cellular repair and targeted delivery., QC 20230613

Hydrogels of cross-linked mucin glycoproteins (Muc-gel) have shown strong immune-modulating properties toward macrophages in vitro, which are translated in vivo by the dampening of the foreign body response to implantation in mice. Beyond mucin hydrogels, other biomaterials such as sensors, electrodes, and other long-term implants would also benefit from such immune-modulating properties. In this work, we aimed to transfer the bioactivity observed for three-dimensional Muc-gels to the surface of two model materials by immobilizing mucin into thin films (Muc-film) using covalent layer-by-layer assembly. We tested how the surface immobilization of mucins affects macrophage responses compared to Muc-gels. We showed that Muc-films on soft polyacrylamide gels mimic Muc-gel in their modulation of macrophage responses with activated gene expression of inflammatory cytokines on day 1 and then dampening them on day 3. Also, the markers of polarized macrophages, M1 and M2, were expressed at the same level for macrophages on Muc-film-coated soft polyacrylamide gels and Muc-gel. In contrast, Muc-film-coated hard polystyrene led to a different macrophage response compared to Muc-gel, having no activated expression of inflammatory cytokines and a different M1 marker expression. This suggested that the substrate mechanical properties and mucin molecular configuration determined by substrate-mucin interactions affect mucin immune-modulating properties. We conclude that mucin immune-modulating properties can be transferred to materials by mucin surface immobilization but will be dependent on the substrate chemical and mechanical properties., QC 20230523

The first part of this thesis pinpointed the outstanding properties of macromolecular lubricants in different scenarios. In the framework of those experiments, a custom-made oscillatory tribology setup was developed, that complements a commercial rotational measuring unit. Example studies in the fields of food engineering and cartilage tribology were conducted and the abilities of macromolecular lubricants to reduce both, friction and wear formation were highlighted. As one particular example, the possibilities and limitations of mucin solutions were further investigated in detail to gain a deeper understanding of the mechanisms that underlie macromolecular lubrication. In the second part, macromolecules were immobilized onto technical polymer surfaces in the form of polymer-brush coatings. In this context, a multi-step coating process was developed that allows to covalently bind mucin glycoproteins onto a variety of medically relevant polymer materials. It was shown, that this coating strategy is capable of creating mechanically stable mucin layers, which can further resist a broad range of physiologically relevant environmental conditions. Moreover, this thesis demonstrated that surface-bound macromolecules can interact with other solubilized macromolecules and that these interactions are mostly of steric nature, i.e. entanglement, and less governed by electrostatic effects. The third part of this thesis continued in the field of macromolecular coatings; however, the viewpoint was shifted from lubrication to creating coatings, that interact directly with their environment. To underline the tuneability of macromolecular coatings, a platform was presented that allows for investigating the selective binding properties of macromolecules in a porous PDMS sponge. Furthermore, it was shown that the mucin coating presented before also exhibits intrinsic anti-biofouling properties, i.e. it reduces the undesirable deposition of proteins, bacteria and fibroblasts. Finally, a, Das Erste von insgesamt drei Kapiteln dieser Dissertation befasst sich mit den herausragenden Eigenschaften makromolekularer Schmiermittel in verschiedenen Szenarien. Zunächst wurde dafür ein tribologischer Messaufbau entwickelt, der es erlaubt, oszillatorische Reibmessungen an einem kommerziellen Scher-Rheometer durchzuführen. Anhand verschiedener Beispiele wurde gezeigt, dass solch makromolekulare Schmiermittel in der Lage sind sowohl Reibung als auch Abrieb auf verschiedenen Oberflächen drastisch zu reduzieren. Dabei wurde ein spezieller Fokus auf das Glykoprotein Mucin gelegt. Verschiedene Versuchsreihen wurden durchgeführt, die einen neuen, tieferen Einblick in das Verständnis makomolekularer Schmierung geben. Im zweiten Teil dieser Arbeit wurden die Makromoleküle, welche zuvor als Additive für wasserbasierte Schmiermittel eingesetzt wurden nun in Form von bürstenartigen Beschichtungen auf technische Kunststoffoberflächen aufgetragen. In diesem Zusammenhang wurde ein mehrstufiger Beschichtungsprozess entwickelt, der es erstmals erlaubt, Mucinmoleküle kovalent auf eine Vielzahl medizinischer Kunststoffe zu koppeln. Es wurde gezeigt, dass diese Strategie mechanisch stabile Beschichtungen erzeugen kann, die außerdem in der Lage sind, verschiedensten physiologischen Bedingungen zu widerstehen. Des Weiteren wurde gezeigt, dass oberflächengebundene Makromoleküle mit anderen Molekülen in der Umgebung interagieren können und dass diese Synergien überwiegend durch sterische Effekte und weniger durch Ladung der Moleküle beeinflusst werden. Auch der dritte und letzte Teil dieser Dissertation beschäftigt sich mit molekularen Beschichtungen, diesmal jedoch nicht zur Reduzierung von Reibung. Stattdessen sollen Beschichtungen nun so gestaltet werden, dass sie aktiv mit der Umgebung interagieren. Um die Vielfältigkeit solch makromolekularer Beschichtungen hervorzuheben wurde zunächst eine Plattform präsentiert, die es ermöglicht das selektive Bindungsverhalten dieser Makomolek

Immune-modulating biomaterials used to encapsulate cells and microtissue transplants can be engineered to dampen the immune reaction and increase treatment efficacy. Mucin-derived materials have gained attention for their ability to modulate macrophage and dendritic cell activity, and to trigger mild foreign body response when implanted in vivo. In this study, the potential of mucin hydrogels (Muc-gels) as cell-encapsulating materials is investigated. When placed in contact with blood, Muc-gels trigger significantly lower complement activation, compared to clinical grade alginate hydrogels. Muc-gel is a size-selective barrier strongly hindering the diffusion of molecules with a hydrodynamic radius larger than 6 nm such as immunoglobulins. Muc-gels support the growth of MIN6m9 insulin-secreting cells into islet-like organoids and the survival of primary human pancreatic islets, which maintained glucose responsiveness. Muc-gels can be shaped into microdroplets in which MIN6m9 cells or cell aggregates can be encapsulated without loss of viability. Microdroplet encapsulation will allow transplants to be easily injected and improve their survival by favoring mass transport through the capsule. The combination of strong immune modulatory properties, appropriate selective barrier profile, biocompatibility for embedded cells Muc-gels of particular value for microencapsulating cells or microtissues for transplantation.

Hydrogels made of crosslinked macromolecules used in regenerative medicine technologies can be designed to affect the fate of surrounding cells and tissues in defined ways. Their function typically depends on the type and number of bioactive moieties such as receptor ligands present in the hydrogel. However, the detail in how such moieties are presented to cells can also be instrumental. In this work, how the crosslinking architecture of a hydrogel can affect its bioactivity is explored. It is shown that bovine submaxillary mucins, a highly glycosylated and immune-modulating protein, exhibit strikingly different bioactivities whether they are crosslinked through their glycans or their protein domains. Both the susceptibility to enzymatic degradation and macrophage response are affected, while rheological properties and barrier to diffusion are mostly unaffected. The results suggest that crosslinking architecture affects the accessibility of the substrate to proteases and the pattern of sialic acid residues exposed to the macrophages. Thus, modulating the accessibility of binding sites through the choice of the crosslinking strategy appears as a useful parameter to tune the bioactivity of hydrogel-based systems., QC 20211110

Commercial mucin glycoproteins are routinely used as a model to investigate the broad range of important functions mucins fulfill in our bodies, including lubrication, protection against hostile germs, and the accommodation of a healthy microbiome. Moreover, purified mucins are increasingly selected as building blocks for multifunctional materials, i.e., as components of hydrogels or coatings. By performing a detailed side-by-side comparison of commercially available and lab-purified variants of porcine gastric mucins, we decipher key molecular motifs that are crucial for mucin functionality. As two main structural features, we identify the hydrophobic termini and the hydrophilic glycosylation pattern of the mucin glycoprotein; moreover, we describe how alterations in those structural motifs affect the different properties of mucins-on both microscopic and macroscopic levels. This study provides a detailed understanding of how distinct functionalities of gastric mucins are established, and it highlights the need for high-quality mucins-for both basic research and the development of mucin-based medical products., QC 20220301

In vitro cancer models that can largely mimic the in vivo microenvironment are crucial for conducting more accurate research. Models of three-dimensional (3D) culture that can mimic some aspects of cancer microenvironment or cancer biopsies that can adequately represent tumor heterogeneity are intensely used currently. Those models still lack the dynamic stress stimuli in gastric carcinoma exposed to stomach peristalsis in vivo. This study leveraged a lab-developed four-dimensional (4D) culture model by a magnetic responsive alginate-based hydrogel to rotating magnets that can mimic stress stimuli in gastric cancer (GC). We used the 4D model to culture human GC cell line AGS and SGC7901, cells at the primary and metastasis stage. We revealed the 4D model altered the cancer cell growth kinetics mechanistically by altering PCNA and p53 expression compared to the 3D culture that lacks stress stimuli. We found the 4D model altered the cancer spheroids stemness as evidenced by enhanced cancer stem cells (CD44) marker expression in AGS spheroids but the expression was dampened in SGC7901 cells. We examined the multi-drug resistance (MDR1) marker expression and found the 4D model dampened the MDR1 expression in SGC7901 cell spheroids, but not in spheroids of AGS cells. Such a model provides the stomach peristalsis mimic and is promising for conducting basic or translational GC-associated research, drug screening, and culturing patient gastric biopsies to tailor the therapeutic strategies in precision medicine., QC 20210524

Gaining control over the delivery of therapeutics to a specific disease site is still very challenging. However, especially when cytotoxic drugs such as chemotherapeutics are used, the importance of a control mechanism that can differentiate "sick" target cells from the surrounding healthy tissue is pivotal. Here, we designed a nanoparticle-based drug delivery process, which releases an active agent only in the presence of a specific trigger DNA sequence. With this strategy, we are able to initiate the release of therapeutics into the cytosol with high efficiency. Furthermore, we demonstrate how an endogenous marker (e.g., a specific miRNA sequence) that is overexpressed in the initial phases of certain cancer types can be used as a stimulus to autonomously initiate intracellular drug release-and only in cells where this pathophysiological marker is present. We expect that this precisely controlled delivery mechanism can facilitate the design of site-specific treatments for such diseases, where an overexpression of signature oligonucleotide sequences has been identified., QC 20210415

The first part of this thesis pinpointed the outstanding properties of macromolecular lubricants in different scenarios. In the framework of those experiments, a custom-made oscillatory tribology setup was developed, that complements a commercial rotational measuring unit. Example studies in the fields of food engineering and cartilage tribology were conducted and the abilities of macromolecular lubricants to reduce both, friction and wear formation were highlighted. As one particular example, the possibilities and limitations of mucin solutions were further investigated in detail to gain a deeper understanding of the mechanisms that underlie macromolecular lubrication. In the second part, macromolecules were immobilized onto technical polymer surfaces in the form of polymer-brush coatings. In this context, a multi-step coating process was developed that allows to covalently bind mucin glycoproteins onto a variety of medically relevant polymer materials. It was shown, that this coating strategy is capable of creating mechanically stable mucin layers, which can further resist a broad range of physiologically relevant environmental conditions. Moreover, this thesis demonstrated that surface-bound macromolecules can interact with other solubilized macromolecules and that these interactions are mostly of steric nature, i.e. entanglement, and less governed by electrostatic effects. The third part of this thesis continued in the field of macromolecular coatings; however, the viewpoint was shifted from lubrication to creating coatings, that interact directly with their environment. To underline the tuneability of macromolecular coatings, a platform was presented that allows for investigating the selective binding properties of macromolecules in a porous PDMS sponge. Furthermore, it was shown that the mucin coating presented before also exhibits intrinsic anti-biofouling properties, i.e. it reduces the undesirable deposition of proteins, bacteria and fibroblasts. Finally, a, Das Erste von insgesamt drei Kapiteln dieser Dissertation befasst sich mit den herausragenden Eigenschaften makromolekularer Schmiermittel in verschiedenen Szenarien. Zunächst wurde dafür ein tribologischer Messaufbau entwickelt, der es erlaubt, oszillatorische Reibmessungen an einem kommerziellen Scher-Rheometer durchzuführen. Anhand verschiedener Beispiele wurde gezeigt, dass solch makromolekulare Schmiermittel in der Lage sind sowohl Reibung als auch Abrieb auf verschiedenen Oberflächen drastisch zu reduzieren. Dabei wurde ein spezieller Fokus auf das Glykoprotein Mucin gelegt. Verschiedene Versuchsreihen wurden durchgeführt, die einen neuen, tieferen Einblick in das Verständnis makomolekularer Schmierung geben. Im zweiten Teil dieser Arbeit wurden die Makromoleküle, welche zuvor als Additive für wasserbasierte Schmiermittel eingesetzt wurden nun in Form von bürstenartigen Beschichtungen auf technische Kunststoffoberflächen aufgetragen. In diesem Zusammenhang wurde ein mehrstufiger Beschichtungsprozess entwickelt, der es erstmals erlaubt, Mucinmoleküle kovalent auf eine Vielzahl medizinischer Kunststoffe zu koppeln. Es wurde gezeigt, dass diese Strategie mechanisch stabile Beschichtungen erzeugen kann, die außerdem in der Lage sind, verschiedensten physiologischen Bedingungen zu widerstehen. Des Weiteren wurde gezeigt, dass oberflächengebundene Makromoleküle mit anderen Molekülen in der Umgebung interagieren können und dass diese Synergien überwiegend durch sterische Effekte und weniger durch Ladung der Moleküle beeinflusst werden. Auch der dritte und letzte Teil dieser Dissertation beschäftigt sich mit molekularen Beschichtungen, diesmal jedoch nicht zur Reduzierung von Reibung. Stattdessen sollen Beschichtungen nun so gestaltet werden, dass sie aktiv mit der Umgebung interagieren. Um die Vielfältigkeit solch makromolekularer Beschichtungen hervorzuheben wurde zunächst eine Plattform präsentiert, die es ermöglicht das selektive Bindungsverhalten dieser Makomolek

Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. An attractive feature is their ability to modulate the immune response, in part by engaging with sialic acid binding receptors on immune cells. Once assembled into hydrogels, bovine submaxillary mucins (Muc gels) were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulation in vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar and then assembling the mucin variants into covalently cross-linked hydrogels with rheological and surface nanomechanical properties similar to nonmodified Muc gels. Results with THP-1 and human primary peripheral blood monocytes derived macrophages showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, for most makers with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications., QC 20200714

The immune-mediated foreign body response to biomaterial implants can trigger the formation of insulating fibrotic capsules that can compromise implant function. To address this challenge, the intrinsic bioactivity of the mucin biopolymer, a heavily glycosylated protein that forms the protective mucus gel covering mucosal epithelia, is leveraged. By using a bioorthogonal inverse electron demand Diels-Alder reaction, mucins are crosslinked into implantable hydrogels. It is shown that mucin hydrogels (Muc-gels) modulate the immune response driving biomaterial-induced fibrosis. Muc-gels do not elicit fibrosis 21 days after implantation in the peritoneal cavity of C57Bl/6 mice, whereas medical-grade alginate hydrogels are covered by fibrous tissues. Further, Muc-gels dampen the recruitment of innate and adaptive immune cells to the gel and trigger a pattern of very mild activation marked by a noticeably low expression of the fibrosis-stimulating transforming growth factor beta 1 cytokine. Macrophages recruited to Muc-gels upregulate the gene expression of the protein inhibitor of activated STAT 1 (PIAS1) and SH2-containing phosphatase 1 (SHP-1) cytokine regulatory proteins, which likely contributes to their low cytokine expression profiles. With this advance in mucin materials, an essential tool is provided to better understand mucin bioactivities and to initiate the development of new mucin-based and mucin-inspired "immune-informed" materials for implantable devices subject to fibrotic encapsulation.

In the human body, mucin glycoproteins efficiently reduce friction between tissues and thereby protect the mucosa from mechanical damage. Mucin lubricity is closely related to their molecular structure: it has been demonstrated previously that the hydrophobic termini of mucins critically contribute to their lubricity. If and how intrinsic sources of negative charge in mucins, e.g., sulfated glycans and sialic acid residues, are relevant for the tribological behavior of mucin solutions has, however, not been addressed yet. In this manuscript, we show that the removal of either sialic acid or sulfate groups, which comprise only a minor amount of the total molecular weight, from MUC5B drastically reduces its lubricity. For MUC5AC solutions, however, this effect only occurs once mucin-associated DNA is removed as well. We find that neither the hydration state nor the average conformation of mucins adsorbed onto hydrophilic or hydrophobic surfaces is affected by the removal of anionic sugars. Instead, our data suggests that a loss of anionic sugars mainly influences the dynamic adsorption process of mucins onto both hydrophilic and hydrophobic surfaces., QC 20200505

The many interesting properties of chitosan polysaccharides have prompted their extensive use as biomaterial building blocks, for instance as antimicrobial coatings, tissue engineering scaffolds, and drug delivery vehicles. The translation of these chitosan-based systems to the clinic still requires a deeper understanding of their safety profiles. For instance, the widespread claim that chitosans are spermicidal is supported by little to no data. Herein, we thoroughly investigate whether chitosan oligomer (CO) molecules can impact the functional and structural features of human spermatozoa. By using a large number of primary sperm cell samples and by isolating the effect of chitosan from the effect of sperm dissolution buffer, we provide the first realistic and complete picture of the effect of chitosans on sperms. We found that CO binds to cell surfaces or/and is internalized by cells and affected the average path velocity of the spermatozoa, in a dose-dependent manner. However, CO did not affect the progressive motility, motility, or sperm morphology, nor did it cause loss of plasma membrane integrity, reactive oxygen species production, or DNA damage. A decrease in spermatozoa adenosine triphosphate levels, which was especially significant at higher CO concentrations, points to possible interference of CO with mitochondrial functions or the glycolysis processes. With this first complete and in-depth look at the spermicidal activities of chitosans, we complement the complex picture of the safety profile of chitosans and inform on further use of chitosans in biomedical applications., QC 20200205