Solid Phase Peptide Synthesis on Chitosan Thin Films.

Stable chitosan thin films can be promising substrates for creating nanometric peptide-bound polyglucosamine layers. Those are of scientific interest since they can have certain structural similarities to bacterial peptidoglycans. Such films were deposited by spin coating from chitosan solutions and modified by acetylation and N-protected amino acids. The masses of deposited materials and their stability in aqueous solutions at different pH values and water interaction were determined with a quartz crystal microbalance with dissipation (QCM-D). The evolution of the surface composition was followed by X-ray photoelectron (XPS) and attenuated total reflectance infrared (ATR-IR) spectroscopy. Morphological changes were measured by atomic force microscopy (AFM), while the surface wettability was monitored by by static water contact angle measurements. The combination of the characterization techniques enabled an insight into the surface chemistry for each treatment step and confirmed the acetylation and coupling of N-protected glycine peptides. The developed procedures are seen as first steps toward preparing thin layers of acetylated chitin, potentially imitating the nanometric peptide substituted glycan layers found in bacterial cell walls.

Humidity Response of Cellulose Thin Films.

Cellulose-water interactions are crucial to understand biological processes as well as to develop tailor made cellulose-based products. However, the main challenge to study these interactions is the diversity of natural cellulose fibers and alterations in their supramolecular structure. Here, we study the humidity response of different, well-defined, ultrathin cellulose films as a function of industrially relevant treatments using different techniques. As treatments, drying at elevated temperature, swelling, and swelling followed by drying at elevated temperatures were chosen. The cellulose films were prepared by spin coating a soluble cellulose derivative, trimethylsilyl cellulose, onto solid substrates followed by conversion to cellulose by HCl vapor. For the highest investigated humidity levels (97%), the layer thickness increased by ca. 40% corresponding to the incorporation of 3.6 molecules of water per anhydroglucose unit (AGU), independent of the cellulose source used. The aforementioned treatments affected this ratio significantly with drying being the most notable procedure (2.0 and 2.6 molecules per AGU). The alterations were investigated in real time with X-ray reflectivity and quartz crystal microbalance with dissipation, equipped with a humidity module to obtain information about changes in the thickness, roughness, and electron density of the films and qualitatively confirmed using grazing incidence small angle X-ray scattering measurements using synchrotron irradiation.

Nano- and Micropatterned Polycaprolactone Cellulose Composite Surfaces with Tunable Protein Adsorption, Fibrin Clot Formation, and Endothelial Cellular Response.

This work describes the interaction of the human blood plasma proteins albumin, fibrinogen, and γ-globulins with micro- and nanopatterned polymer interfaces. Protein adsorption studies were correlated with the fibrin clotting time of human blood plasma and with the growth of primary human pulmonary artery endothelial cells (hECs) on these patterns. It was observed that blends of polycaprolactone (PCL) and trimethylsilyl-protected cellulose form various thin-film patterns during spin coating, depending on the mass ratio of the polymers in the spinning solutions. Vapor-phase acid-catalyzed deprotection preserves these patterns but yields interfaces that are composed of hydrophilic cellulose domains enclosed by hydrophobic PCL. The blood plasma proteins are repelled by the cellulose domains, allowing for a suggested selective protein deposition on the PCL domains. An inverse proportional correlation is observed between the amount of cellulose present in the films and the mass of irreversibly adsorbed proteins. This results in significantly increased fibrin clotting times and lower masses of deposited clots on cellulose-containing films as revealed by quartz crystal microbalance with dissipation measurements. Cell viability of hECs grown on these surfaces was directly correlated with higher protein adsorption and faster clot formation. The results show that presented patterned polymer composite surfaces allow for a controllable blood plasma protein coagulation and a significant biological response from hECs. It is proposed that this knowledge can be utilized in regenerative medicine, cell cultures, and artificial vascular grafts by a careful choice of polymers and patterns.

Multilayered Polysaccharide Nanofilms for Controlled Delivery of Pentoxifylline and Possible Treatment of Chronic Venous Ulceration.

Local drug delivery systems made from nontoxic polysaccharide nanofilms have an enormous potential in wound care. A detailed understanding of the structural, surface, physicochemical, and cytotoxic properties of such systems is crucial to design clinically efficacious materials. Herein, we fabricated polysaccharide-based nanofilms onto either a 2D model (SiO2 and Au sensors) or on nonwoven alginate 3D substrates using an alternating assembly of N,N,N-trimethylchitosan (TMC) and alginic acid (ALG) by a spin-assisted layer-by-layer (LbL) technique. These TMC/ALG multilayered nanofilms are used for a uniform encapsulation and controlled release of pentoxifylline (PTX), a potent anti-inflammatory drug for treatment of the chronic venous ulceration. We show a tailorable film growth and mass, morphology, as well as surface properties (charge, hydrophilicity, porosity) of the assembled nanofilms through control of the coating during the spin-assisted assembly. The uniform distribution of the encapsulated PTX in the TMC/ALG nanofilms is preserved even with when the amount of the incorporated PTX increases. The PTX release mechanism from the model and real systems is studied in detail and is very comparable for both systems. Finally, different cell-based assays illustrated the potential of the TMC/ALG multilayer system in wound care (e.g., treatment chronic venous ulceration) applications, including a decrease of TNF-α secretion, a common indicator of inflammation.

Interaction of Tissue Engineering Substrates with Serum Proteins and Its Influence on Human Primary Endothelial Cells.

Polymer-based biomaterials particularly polycaprolactone (PCL) are one of the most promising substrates for tissue engineering. The surface chemistry of these materials plays a major role since it governs protein adsorption, cell adhesion, viability, degradation, and biocompatibility in the first place. This study correlates the interaction of the most abundant serum proteins (albumin, immunoglobulins, fibrinogen) with the surface properties of PCL and its influence on the morphology and metabolic activity of primary human arterial endothelial cells that are seeded on the materials. Prior to that, thin films of PCL are manufactured by spin-coating and characterized in detail. A quartz crystal microbalance with dissipation (QCM-D), a multiparameter surface plasmon resonance spectroscopy instrument (MP-SPR), wettability data, and atomic force microscopy are combined to elucidate the pH-dependent protein adsorption on the PCL substrates. Primary endothelial cells are cultured on the protein modified polymer, and conclusions are drawn on the significant impact of type and form of proteins coatings on cell morphology and metabolic activity.

Exploring Nonspecific Protein Adsorption on Lignocellulosic Amphiphilic Bicomponent Films.

In this contribution, we explore the interaction of lignocellulosics and proteins aiming at a better understanding of their synergistic role in natural systems. In particular, the manufacturing and characterization of amphiphilic bicomponent thin films composed of hydrophilic cellulose and a hydrophobic lignin ester in different ratios is presented which may act as a very simplified model for real systems. Besides detailed characterizations of the films and mechanisms to explain their formation, nonspecific protein adsorption using bovine serum albumin (BSA) onto the films was studied using a quartz crystal microbalance with dissipation (QCM-D). As it turns out, the rather low nonspecific protein adsorption of BSA on cellulose is further reduced when these hydrophobic lignins are incorporated into the films. The lignin ester acts in these blend films as sacrificial component, probably via an emulsification mechanism. Additionally, the amphiphilicity of the films may prevent the adsorption of BSA as well. Although there are some indications, it remains unclear whether any kind of protein interactions in such systems are of specific nature.

Designing Hydrophobically Modified Polysaccharide Derivatives for Highly Efficient Enzyme Immobilization.

In this contribution, a hydrophobically modified polysaccharide derivative is synthesized in an eco-friendly solvent water by conjugation of benzylamine with the backbone of the biopolymer. Owing to the presence of aromatic moieties, the resulting water-soluble polysaccharide derivative self-assembles spontaneously and selectively from solution on the surface of nanometric thin films and sheets of polystyrene (PS). The synthetic polymer modified in this way bears a biocompatible nanolayer suitable for the immobilization of horseradish peroxidase (HRP), a heme-containing metalloenzyme often employed in biocatalysis and biosensors. Besides the detailed characterization of the polysaccharide derivative, a quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) are used to investigate the binding efficiency and interaction of HRP with the tailored polysaccharide interfaces. Subsequent enzyme activity tests reveal details of the interaction of HRP with the solid support. The novel polysaccharide derivative and its use as a material for the selective modification of PS lead to a beneficial, hydrophilic environment for HRP, resulting in high enzymatic activities and a stable immobilization of the enzyme for biocatalytic and analytic purposes.

Triggering protein adsorption on tailored cationic cellulose surfaces.

The equipment of cellulose ultrathin films with BSA (bovine serum albumin) via cationization of the surface by tailor-made cationic celluloses is described. In this way, matrices for controlled protein deposition are created, whereas the extent of protein affinity to these surfaces is controlled by the charge density and solubility of the tailored cationic cellulose derivative. In order to understand the impact of the cationic cellulose derivatives on the protein affinity, their interaction capacity with fluorescently labeled BSA is investigated at different concentrations and pH values. The amount of deposited material is quantified using QCM-D (quartz crystal microbalance with dissipation monitoring, wet mass) and MP-SPR (multi-parameter surface plasmon resonance, dry mass), and the mass of coupled water is evaluated by combination of QCM-D and SPR data. It turns out that adsorption can be tuned over a wide range (0.6-3.9 mg dry mass m(-2)) depending on the used conditions for adsorption and the type of employed cationic cellulose. After evaluation of protein adsorption, patterned cellulose thin films have been prepared and the cationic celluloses were adsorbed in a similar fashion as in the QCM-D and SPR experiments. Onto these cationic surfaces, fluorescently labeled BSA in different concentrations is deposited by an automatized spotting apparatus and a correlation between the amount of the deposited protein and the fluorescence intensity is established.

Films based on TEMPO-oxidized chitosan nanoparticles: Obtaining and potential application as wound dressings.

A series of novel films based on TEMPO-oxidized chitosan nanoparticles were prepared by casting method. Fourier transform infrared spectroscopy (FTIR) was employed to ascertain the chemical structure of TEMPO-oxidized chitosan. The surface morphology of the TEMPO-oxidized chitosan nanoparticles was analyzed by atomic force microscopy (AFM). The physicochemical (area density, thickness, iodine sorption, roughness), functional (moisture sorption, liquid absorption capacity, weight loss upon contact with the liquid, and water vapor transmission rate), antibacterial, and antioxidant properties of films based on TEMPO-oxidized chitosan nanoparticles were also investigated. The physicochemical properties of the films varied widely: area density ranged from 77.83 ± 0.06 to184.46 ± 0.05 mg/cm2, thickness varied between 80.5 ± 1.6 and 200.5 ± 1.6 µm, iodine sorption spanned from 333.7 ± 2.1 to166.4 ± 2.2 mg I2/g, and roughness ranged from 4.1 ± 0.2 to 5.6 ± 0.3 nm. Similarly, the functional properties also varied significantly: moisture sorption ranged from 4.76 ± 0.03 to 9.62 ± 0.11 %, liquid absorption capacity was between 129.04 ± 0.24 and 159.33 ± 0.73 % after 24 h, weight loss upon contact with the liquid varied between 31.06 ± 0.35 and 45.88 ± 0.58 % after 24 h and water vapor transmission rate ranged from 1220.10 ± 2.91to1407.77 ± 5.22 g/m2 day. Despite the wide variations in physicochemical and functional properties, all films showed maximum bacterial reduction of Staphylococcus aureus and Escherichia coli, although they exhibited low antioxidant activity. The results suggest that the films could be effectively utilized as antibacterial wound dressings.

Hyaluronic acid conjugates of glycine peptides and L-tryptophan.

This work reports about the conjugation of glycine C-terminal ethyl and methyl ester peptides and L-tryptophan methyl ester with sodium hyaluronate in aqueous solutions using the peptide coupling agent DMTMM (or short DMT, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride). Detailed infrared (IR) absorbance and 1H and 13C (2D) NMR studies (heteronuclear multi-bond correlation spectroscopy, HMBC) confirmed covalent and regioselective amide bonds with the D-glucuronate, but also proves the presence of DMT traces in all conjugates. The ethyl ester`s methyl protons on the peptides` C-terminal could be used to quantify the degree of substitution of the peptide on the hyaluronate scaffold by NMR. The ester group also proved stable during conjugation and work-up, and could in some cases be selectively cleaved in water whilst leaving the amide bond intact as shown by potentiometric charge titration, NMR and IR. The conjugates did not influence the capability of human umbilical vein endothelial cells (HUVECs) to reduce MTS (5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-2-thiazolyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt) to a formazan dye, which points towards a low cytotoxicity for the obtained products. The conjugation method and products could be tested for tissue engineering gels or drug delivery purposes with alternative, biologically active peptides.

4-Axis 3D-Printed Tubular Biomaterials Imitating the Anisotropic Nanofiber Orientation of Porcine Aortae.

Many of the peculiar properties of the vasculature are related to the arrangement of anisotropic proteinaceous fibers in vessel walls. Understanding and imitating these arrangements can potentially lead to new therapies for cardiovascular diseases. These can be pre-surgical planning, for which patient-specific ex vivo anatomical models for endograft testing are of interest. Alternatively, therapies can be based on tissue engineering, for which degradable in vitro cell growth substrates are used to culture replacement parts. In both cases, materials are desirable that imitate the biophysical properties of vessels, including their tubular shapes and compliance. This work contributes to these demands by offering methods for the manufacturing of anisotropic 3D-printed nanofibrous tubular structures that have similar biophysical properties as porcine aortae, that are biocompatible, and that allow for controlled nutrient diffusion. Tubes of various sizes with axial, radial, or alternating nanofiber orientation along the blood flow direction are manufactured by a customized method. Blood pressure-resistant, compliant, stable, and cell culture-compatible structures are obtained, that can be degraded in vitro on demand. It is suggested that these healthcare materials can contribute to the next generation of cardiovascular therapies of ex vivo pre-surgical planning or in vitro cell culture.

Generalized indirect Fourier transformation as a valuable tool for the structural characterization of aqueous nanocrystalline cellulose suspensions by small angle X-ray scattering.

Small angle X-ray scattering (SAXS) is employed to characterize the inner structure and shape of aqueous nanocrystalline cellulose suspensions using the generalized indirect Fourier transformation (GIFT). The use of the GIFT approach provides a single fitting procedure for the determination of intra- and interparticle interactions due to a simultaneous treatment of the form factor P(q) and the structure factor S(q). Moreover, GIFT allows for the determination of particle charges and polydispersity indices. As test material, aqueous nanocrystalline cellulose suspensions (aNCS) prepared by the H2SO4 route have been investigated and characterized (SAXS, dynamic light scattering, zeta potential).

3D-Printed Collagen-Nanocellulose Hybrid Bioscaffolds with Tailored Properties for Tissue Engineering Applications.

Hybrid collagen (Coll) bioscaffolds have emerged as a promising solution for tissue engineering (TE) and regenerative medicine. These innovative bioscaffolds combine the beneficial properties of Coll, an important structural protein of the extracellular matrix, with various other biomaterials to create platforms for long-term cell growth and tissue formation. The integration or cross-linking of Coll with other biomaterials increases mechanical strength and stability and introduces tailored biochemical and physical factors that mimic the natural tissue microenvironment. This work reports on the fabrication of chemically cross-linked hybrid bioscaffolds with enhanced properties from the combination of Coll, nanofibrillated cellulose (NFC), carboxymethylcellulose (CMC), and citric acid (CA). The bioscaffolds were prepared by 3D printing ink containing Coll-NFC-CMC-CA followed by freeze-drying, dehydrothermal treatment, and neutralization. Cross-linking through the formation of ester bonds between the polymers and CA in the bioscaffolds was achieved by exposing the bioscaffolds to elevated temperatures in the dry state. The morphology, pores/porosity, chemical composition, structure, thermal behavior, swelling, degradation, and mechanical properties of the bioscaffolds in the dry and wet states were investigated as a function of Coll concentration. The bioscaffolds showed no cytotoxicity to MG-63 human bone osteosarcoma cells as tested by different assays measuring different end points. Overall, the presented hybrid Coll bioscaffolds offer a unique combination of biocompatibility, stability, and structural support, making them valuable tools for TE.

Adsorption of carboxymethyl cellulose on polymer surfaces: evidence of a specific interaction with cellulose.

The adsorption of carboxymethyl cellulose (CMC), one of the most important cellulose derivatives, is crucial for many scientific investigations and industrial applications. Especially for surface modifications and functionalization of materials, the polymer is of interest. The adsorption properties of CMC are dependent not only on the solutions state, which can be influenced by the pH, temperature, and electrolyte concentration, but also on the chemical composition of the adsorbents. We therefore performed basic investigation studies on the interaction of CMC with a variety of polymer films. Thin films of cellulose, cellulose acetate, deacetylated cellulose acetate, polyethylene terephthalate, and cyclo olefin polymer were therefore prepared on sensors of a QCM-D (quartz crystal microbalance) and on silicon substrates. The films were characterized with respect to the thickness, wettability, and chemical composition. Subsequently, the interaction and deposition of CMC in a range of pH values without additional electrolyte were measured with the QCM-D method. A comparison of the QCM-D results showed that CMC is favorably deposited on pure cellulose films and deacetylated cellulose acetate at low pH values. Other hydrophilic surfaces such as silicon dioxide or polyvinyl alcohol coated surfaces did not adsorb CMC to a significant extent. Atomic force microcopy confirmed that the morphology of the adsorbed CMC layers differed depending on the substrate. On hydrophobic polymer films, CMC was deposited in the form of larger particles in lower amounts whereas hydrophilic cellulose substrates were to a high extent uniformly covered by adsorbed CMC. The chemical similarity of the CMC backbone seems to favor the irreversible adsorption of CMC when the molecule is almost uncharged at low pH values. A selectivity of the cellulose CMC interaction can therefore be assumed. All CMC treated polymer films exhibited an increased hydrophilicity, which confirmed their modification with the functional molecule.

Polysaccharide peptide conjugates: Chemistry, properties and applications.

The intention of this publication is to give an overview on research related to conjugates of polysaccharides and peptides. Dextran, chitosan, and alginate were selected, to cover four of the most often encountered functional groups known to be present in polysaccharides. These groups are the hydroxyl, the amine, the carboxyl, and the acetal functionality. A collection of the commonly used chemical reactions for conjugation is provided. Conjugation results into distinct properties compared to the parent polysaccharide, and a number of these characteristics are highlighted. This review aims at demonstrating the applicability of said conjugates with a strong emphasis on biomedical applications, drug delivery, biosensing, and tissue engineering. Some suggestions are made for more rigorous chemistries and analytics that could be investigated. Finally, an outlook is given into which direction the field could be developed further. We hope that this survey provides the reader with a comprehensive summary and contributes to the progress of works that aim at synthetically combining two of the main building blocks of life into supramolecular structures with unprecedented biological response.

Nano-fibrillated cellulose-based scaffolds for enzyme (co)-immobilization: Application to natural product glycosylation by Leloir glycosyltransferases.

Polysaccharide-based scaffolds are promising carriers for enzyme immobilization. Here, we demonstrate a porous scaffold prepared by direct-ink-writing 3D printing of an ink consisting of nanofibrillated cellulose, carboxymethyl cellulose and citric acid for immobilization application. Negative surface charge introduced by the components made the scaffold amenable for an affinity-like immobilization via the cationic protein module Zbasic2. Zbasic2 fusions of two sugar nucleotide-dependent glycosyltransferases (C-glycosyltransferase, Z-CGT; sucrose synthase, Z-SuSy) were immobilized individually, or co-immobilized, and applied to synthesize the natural C-glycoside nothofagin. The cascade reaction involved ß-C-glycosylation of phloretin (10 mM, ~90 % conversion) from UDP-glucose, provided from sucrose and catalytic amounts of UDP (1.0 mM). Enzymes were co-immobilized at ~65 mg protein/g carrier to receive activities of 9.5 U/g (Z-CGT) and 4.5 U/g (Z-SuSy) in 22-33 % yield (protein) and an effectiveness of 23 % (Z-CGT) and 13 % (Z-SuSy). The scaffold-bound enzymes were recyclable for 5 consecutive reactions.

3D Printed Porous Nanocellulose-Based Scaffolds As Carriers for Immobilization of Glycosyltransferases.

Biocatalysis is increasingly becoming an alternative method for the synthesis of industrially relevant complex molecules. This can be realized by using enzyme immobilized polysaccharide-based 3D scaffolds as compatible carriers, with defined properties. Especially, immobilization of either single or multiple enzymes on a 3D printed polysaccharide scaffold, exhibiting well-organized interconnected porous structure and morphology, is a versatile approach to access the performance of industrially important enzymes. Here, we demonstrated the use of nanocellulose-based 3D porous scaffolds for the immobilization of glycosyltransferases, responsible for glycosylation in natural biosynthesis. The scaffolds were produced using an ink containing nanofibrillated cellulose (NFC), carboxymethyl cellulose (CMC), and citric acid. Direct-ink-writing 3D printing followed by freeze-drying and dehydrothermal treatment at elevated temperature resulted in chemically cross-linked scaffolds, featuring tunable negative charges (2.2-5.0 mmol/g), pore sizes (10-800 µm), fluid uptake capacity, and exceptional dimensional and mechanical stability in the wet state. The negatively charged scaffolds were applied to immobilize two sugar nucleotide-dependent glycosyltransferases (C-glycosyltransferase, Zbasic2-CGT; sucrose synthase, Zbasic2-SuSy), each harboring a cationic binding module (Zbasic2) to promote charge-based enzyme adsorption. Both enzymes were immobilized at ∼30 mg of protein/g of dry carrier (∼20% yield), independent of the scaffold used. Their specific activities were 0.50 U/mg (Zbasic2-CGT) and 0.19 U/mg (Zbasic2-SuSy), corresponding to an efficacy of 37 and 18%, respectively, compared to the soluble enzymes. The glycosyltransferases were coimmobilized and shown to be active in a cascade reaction to give the natural C-glycoside nothofagin from phloretin (1.0 mM; ∼95% conversion). All enzyme bound scaffolds showed reusability of a maximum of 5 consecutive reactions. These results suggest that the 3D printed and cross-linked NFC/CMC-based scaffolds could present a class of solid carriers for enzyme (co)-immobilization, with promising applications in glycosyltransferase-catalyzed synthesis and other fields of biocatalysis.

Organic acid cross-linked 3D printed cellulose nanocomposite bioscaffolds with controlled porosity, mechanical strength, and biocompatibility.

Herein, we fabricated chemically cross-linked polysaccharide-based three-dimensional (3D) porous scaffolds using an ink composed of nanofibrillated cellulose, carboxymethyl cellulose, and citric acid (CA), featuring strong shear thinning behavior and adequate printability. Scaffolds were produced by combining direct-ink-writing 3D printing, freeze-drying, and dehydrothermal heat-assisted cross-linking techniques. The last step induces a reaction of CA. Degree of cross-linking was controlled by varying the CA concentration (2.5-10.0 wt.%) to tune the structure, swelling, degradation, and surface properties (pores: 100-450 µm, porosity: 86%) of the scaffolds in the dry and hydrated states. Compressive strength, elastic modulus, and shape recovery of the cross-linked scaffolds increased significantly with increasing cross-linker concentration. Cross-linked scaffolds promoted clustered cell adhesion and showed no cytotoxic effects as determined by the viability assay and live/dead staining with human osteoblast cells. The proposed method can be extended to all polysaccharide-based materials to develop cell-friendly scaffolds suitable for tissue engineering applications.

One-Step Fabrication of Hollow Spherical Cellulose Beads: Application in pH-Responsive Therapeutic Delivery.

The path to greater sustainability and the development of polymeric drug delivery systems requires innovative approaches. The adaptation and use of biobased materials for applications such as targeted therapeutic delivery is, therefore, in high demand. A crucial part of this relates to the development of porous and hollow structures that are biocompatible, pH-responsive, deliver active substances, and contribute to pain relief, wound healing, tissue regeneration, and so forth. In this study, we developed a facile single-step and water-based method for the fabrication of hollow spherical cellulose beads for targeted drug release in response to external pH stimuli. Through base-catalyzed deprotection, hydrophobic solid and spherical cellulose acetate beads are transformed into hydrophilic cellulose structures with a hollow interior (wall thickness: 150 µm and inner diameter: 650 µm) by a stepwise increment of temperature and treatment time. Besides the pH-responsive fluid uptake properties, the hollow cellulose structures exhibit a maximum encapsulation efficiency of 20-85% diclofenac (DCF), a nonsteroidal anti-inflammatory drug, used commonly to treat pain and inflammatory diseases. The maximum amount of DCF released in vitro increased from 20 to 100% when the pH of the release medium increased from pH 1.2 to 7.4. As for the DCF release patterns and kinetic models at specific pH values, the release showed a diffusion- and swelling-controlled profile, effortlessly fine-tuned by external environmental pH stimuli. Overall, we show that the modified beads exhibit excellent characteristics for transport across the gastrointestinal tract and enhance the bioavailability of the drug. Their therapeutic efficacy and biocompatibility are also evident from the studies on human fibroblast cells. We anticipate that this platform could support and inspire the development of novel sustainable and effective polysaccharide-based delivery systems.

Cellulose-based biogenic supports, remarkably friendly biomaterials for proteins and biomolecules.

Cellulose has a long history dating back to ancient times in the evolution of humanity. It was a key material for basic needs, especially for the construction of shelters, paper making, which allowed our ancestors to perpetuate the valuable literary, philosophical or artistic works. In modern era, cellulose has acquired new dimensions of knowledge and scientific interest. This increased interest in cellulose is due to the need to exploit the still unknown resources that cellulose provides us, possibly due to the remarkable progress made lately in the field of fine characterization of the structure using sophisticated electron microscopes and other characterization techniques that have recently emerged. The growing demands of modern society in the direction of computerization and technology, have led the general interest to move from the classical writing paper to other types of "papers" that incorporates a high degree of ingenuity and intelligence, the so-called special papers, ranging from sensors, chips, motherboards, papers with a high degree of security, and many others. Among these, paper-based biosensors are of special interest, due to their high selectivity, simplicity, low price, and fast response. In this article we will review the new trends in the immobilization of biomolecules on various cellulose-based supports. In the first part, we will discuss the stages prior to the manufacture of a such support by specific chemical modification of the cellulosic substrate, followed by an overview of the most studied proteins, but also the most commonly used methods in monitoring protein adsorption on cellulosic substrates.