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Pectin-based inks development for 3D bioprinting of scaffolds
Abstract
3D bioprinting allows creative ideas for 3D scaffold development. Therefore, it enhances the creation of customized dressings for tissue regeneration and the wound healing process. A relevant requirement when employing hydrogels in extrusion-based bioprinting (EBB), is to maintain design fidelity and shape of printed structures. In this work, three novel biopolymeric inks were formulated of which components are pectin (Pe) with the addition of carboxymethylcellulose (CMC) and microcrystalline cellulose (MCC). Specific methods for study extrudability, printability, physicochemical properties, and cytotoxicity of inks and 3D structures were proposed. 3D models of medium and high printing complexity were developed. Pe + MCC scaffold presents the best square interconnected channels (Printability≈ 1). Young’s modulus of Pe and Pe + MCC scaffolds are in the same range of values as the skin modulus. Pe scaffold presents the highest water retention capacity. From the cytotoxicity test, the three inks showed well in vitro biocompatibility with L929 fibroblast cells. These results suggest that Pe and Pe + MCC biopolymer inks can potentially be implemented for developing 3D printed personalized dressings for wound healing treatment.
... Pectin/MCC bio-ink exhibits the best square interconnected channels (Printability≈ 1). The results revealed its potential use as a personalized wound dressing [76]. Likewise, varying concentrations of CMC-based aqueous hydrogels were printed and lyophilized. ...
... Consequently, pectin can effectively mimic the characteristics of diverse natural tissues. In the realm of tissue engineering, the utilization of pectin in conjunction with calcium carbonate scaffolds and chitin derivatives has been observed to facilitate cell proliferation in a range of cell types, such as human dermal fibroblasts, L929, and NIH3T3 [68]. The addition of pure pectin to hydrogels based on alginate and pluronic will reduce the inflammatory reaction in cell replacement treatments, which were then implanted in mice. ...
... Polymers are commonly used as the material for drug delivery systems due to their biocompatibility, biodegradability, and ability to be tuned for specific drug release kinetics. Some common polymers recently explored in 3D printing for drug delivery include poly(lactic-co-glycolic acid) [13], polycaprolactone [13], polyethylene glycol [14], chitosan [15], pectin [16], carboxymethyl cellulose [17], and MS [18]. These polymers can be formulated into various types of drug delivery systems, including microparticles, nanoparticles, and scaffolds. ...
Nanoporous materials are categorized as microporous (pore sizes 0.2-2 nm), mesoporous (pore sizes 2-50 nm), and macropo-rous (pore sizes 50-1000 nm). Mesoporous silica (MS) has gained a significant interest due to its notable characteristics, including organized pore networks, specific surface areas, and the ability to be integrated in a variety of morphologies. Recently, MS has been widely accepted by range of manufacturer and as drug carrier. Moreover, silica nanoparticles containing mesopores, also known as mesoporous silica nanoparticles (MSNs), have attracted widespread attention in additive manufacturing (AM). AM commonly known as three-dimensional printing is the formalized rapid prototyping (RP) technology. AM techniques, in comparison to conventional methods, aid in reducing the necessity for tooling and allow versatility in product and design customization. There are generally several types of AM processes reported including VAT polymerization (VP), powder bed fusion (PBF), sheet lamination (SL), material extrusion (ME), binder jetting (BJ), direct energy deposition (DED), and material jetting (MJ). Furthermore, AM techniques are utilized in fabrication of various classified fields such as architectural modeling, fuel cell manufacturing, lightweight machines, medical, and fabrication of drug delivery systems. The review concisely elaborates on applications of mesoporous silica as versatile material in fabrication of various AM-based pharmaceutical products with an elaboration on various AM techniques to reduce the knowledge gap.
Skin tissue engineering and regeneration aim at repairing defective skin injuries and progress in wound healing. Until now, even though several developments are made in this field, it is still challenging to face the complexity of the tissue with current methods of fabrication. In this review, short, state-of-the-art on developments made in skin tissue engineering using 3D bioprinting as a new tool are described. The current bioprinting methods and a summary of bioink formulations, parameters, and properties are discussed. Finally, a representative number of examples and advances made in the field together with limitations and future needs are provided.
This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field.
Regardless of the considerable progress in properties and versatility of synthetic polymers, their low biodegradability and lack of environmentally-friendly character remains a critical issue. Pectin is a natural-based polysaccharide contained in the cell walls of many plants allowing their growth and cell extension. This biopolymer can be extracted from plants and isolated as a bioplastic material with different applications, including food packaging. This review aims to present the latest research results regarding pectin, including the structure, different types, natural sources and potential use in several sectors, particularly in food packaging materials. Many researchers are currently working on a multitude of food and beverage industry applications related to pectin as well as combinations with other biopolymers to improve some key properties, such as antioxidant/antimicrobial performance and flexibility to obtain films. All these advances are covered in this review.
Wound healing is an unmet therapeutic challenge among medical society since wound assessment and management is a complex procedure including several factors playing major role in healing process. Wounds can mainly be categorized as acute or chronic. It is well referred that the acute wound displays normal wound physiology while healing, in most cases, is seemed to progress through the normal phases of wound healing. On the other hand, a chronic wound is physiologically impaired. The main problem in wound management is that the majority of wounds are colonized with microbes, whereas this does not mean that all wounds will be infected. In this review, we address the problems that clinicians face to manage while treat acute and chronic wounds. Moreover, we demonstrate the pathophysiology, etiology, prognosis and microbiology of wounds. We further introduce the state of art in pharmaceutical technology field as part of wound management aiming to assist health professionals to overcome the current implications on wound assessment. In addition, authors review researches which included the use of gels and dermal films as wound healing agents. It can be said that natural and synthetic drugs or carriers provide promising solutions in order to meet the wound management standards. However, are the current strategies as desirable as medical society wish?
Nowadays, biopolymers as intelligent and active biopolymer systems in the food and pharmaceutical industry are of considerable interest in their use. With this association in view, biopolymers such as chitosan, alginate, pectin, cellulose, agarose, guar gum, agar, carrageenan, gelatin, dextran, xanthan, and other polymers have received significant attention in recent years due to their abundance and natural availability. Furthermore, their versatile properties such as non-toxicity, biocompatibility, biodegradability, and flexibility offer significant functionalities with multifunctional applications. The purpose of this review is to summarize the most compatible biopolymers such as chitosan, alginate, and pectin, which are used for application in food, biotechnological processes, and biomedical applications. Therefore, chitosan, alginate, and pectin are biopolymers (used in the food industry as a stabilizing, thickening, capsular agent, and packaging) with great potential for future developments. Moreover, this review highlights their characteristics, with a particular focus on their potential for biocompatibility, biodegradability, bioadhesiveness, and their limitations on certain factors in the human gastrointestinal tract.
Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.
Rheological properties and gel characteristics of Sparassis crispa polysaccharides (SCPs) were investigated under various concentrations, temperature, pH, salt concentrations, and sucrose concentrations. SCP solutions behaved as shear thinning pseudoplastic fluids; apparent viscosity increased with concentrations but decreased with extreme conditions and was highest for 1% SCPs at 80 ℃ under neutral conditions; 5% SCPs solutions formed a hysteresis loop and exhibited thixotropic properties. By oscillatory measurements, SCPs were viscoelastic materials. 0.5% and 1% SCPs solutions exhibited viscous behavior at low frequency and enhanced elastic property with the oscillation frequency increased. With the concentration increased to 3% and 5%, the elastic property was predominant in solutions and exhibited gel-like behavior. SCPs gel textural properties and water holding capacity increased with concentration (to 20%) and decreased with salinity, extreme sucrose, and pH. 10% SCPs gels were optimized at 10% sucrose in neutral conditions. Thus, these results implied SCPs had the potential utilization as a new hydrocolloid source in food industries.
Incorporating reinforcement into the practice of digital concrete construction, often called 3D-concrete-printing, is a prerequisite for wide-ranging, structural applications of this new technology. Strain-Hardening Cement-based Composites (SHCC) offer one possible solution to this challenge. In this work, printable SHCC were developed and tested. The composites could be extruded through a nozzle of a 3D-printer so that continuous filaments could be deposited, one upon the other, to build lab-scaled wall specimens without noticeable deformation of the bottom layers. The specimens extracted from the printed walls exhibited multiple fine cracks and pronounced strain-hardening characteristics under uniaxial tensile loading, even for fiber volume fractions as low as 1.0%. In fact, the strain-hardening characteristics of printed specimens were superior to those of mold-cast SHCC specimens.
Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to produce scaffolds with intricate porous geometries that were not feasible with traditional manufacturing processes. Researchers can control the structural geometry through a wide range of customisable printing parameters and design choices including material, print path, temperature, and many other process parameters. Currently, the impact of these choices is not fully understood. This review focuses on how the position and orientation of extruded filaments, which sometimes referred to as the print path, lay-down pattern, or simply “scaffold design”, affect scaffold properties and biological performance. By analysing trends across multiple studies, new understanding was developed on how filament position affects mechanical properties. Biological performance was also found to be affected by filament position, but a lack of consensus between studies indicates a need for further research and understanding. In most research studies, scaffold design was dictated by capabilities of additive manufacturing software rather than free-form design of structural geometry optimised for biological requirements. There is scope for much greater application of engineering innovation to additive manufacture novel geometries. To achieve this, better understanding of biological requirements is needed to enable the effective specification of ideal scaffold geometries.
Chronic non-healing wounds challenge tissue regeneration and impair infection regulation for patients afflicted with this condition. Next generation wound care technology capable of in situ physiological surveillance which can diagnose wound parameters, treat various chronic wound symptoms, and reduce infection at the wound noninvasively with the use of a closed loop therapeutic system would provide patients with an improved standard of care and an accelerated wound repair mechanism. The indicating biomarkers specific to chronic wounds include blood pressure, temperature, oxygen, pH, lactate, glucose, interleukin-6 (IL-6), and infection status. A wound monitoring device would help decrease prolonged hospitalization, multiple doctors' visits, and the expensive lab testing associated with the diagnosis and treatment of chronic wounds. A device capable of monitoring the wound status and stimulating the healing process is highly desirable. In this review, we discuss the impaired physiological states of chronic wounds and explain the current treatment methods. Specifically, we focus on improvements in materials, platforms, fabrication methods for wearable devices, and quantitative analysis of various biomarkers vital to wound healing progress.
Microcrystalline cellulose grafted polycaprolactone (MCC-g-PCL) was successfully synthesized by ring-opening copolymerization catalyzed by 4-dimethylaminopyridine in a dual tetrabutylammonium acetate/dimethyl sulfoxide solvent system. A novel ultraviolet-shielding film based on MCC-g-PCL was prepared by introducing graphene oxide (GO). The results obtained showed that the introduction of GO not only obviously influenced the inherent structure of the MCC-g-PCL but remarkably changed the surface morphology of the composite film. Moreover, the GO/MCC-g-PCL composite showed a significant improvement in tensile strength, from 2.63 to 4.55 MPa, as well as elongation-at-break, from 6.4% to 15.5%, compared with the pure MCC-g-PCL film, owing to the strong hydrogen-bonding interaction that physically crosslinked GO with MCC-g-PCL. Importantly, GO/MCC-g-PCL composite films offered an effective high-energy light-shielding capacity; in particular MCC-g-PCL film containing 1.0 wt% GO possessed good absorbance between 200 nm and 300 nm. This study provides a framework for developing cellulose-based ultraviolet-shielding polymers and better understanding the ultraviolet-shielding mechanism.
Featured Application
Bioprinting of complex cell-laden tissue constructs that mimic the human vascular tissue structure.
Abstract
Microextrusion-based bioprinting within a support bath material is an emerging additive manufacturing paradigm for complex three-dimensional (3D) tissue construct fabrication. Although a support bath medium enables arbitrary in-process geometries to be printed, a significant challenge lies in preserving the shape fidelity upon the extraction of the support bath material. Based on the bioprinting in a support bath paradigm, this paper advances quantitative analyses to systematically determine the printability of cell-laden liquid hydrogel precursors towards filament-based tissue constructs. First, a yield stress nanoclay material is judiciously selected as the support bath medium owing to its insensitivity to temperature and ionic variations that are considered in the context of the current gelatin-alginate bio-ink material formulation. Furthermore, phenomenological observations for the rheology-mediated print outcomes enable the compositions for the bio-ink material (10% gelatin, 3% alginate), in tandem with the support bath medium (4% nanoclay, 0.5% CaCl2), to be identified. To systematically evaluate the performance outcomes for bioprinting within a support bath, this paper advances an experimental parametric study to optimize the 3D structural shape fidelity by varying parameters such as the layer height, extrusion flowrate, printing temperature, and printhead speed, towards fabricating complex 3D structures with the stabilization of the desired shape outcome. Specifically, it is found that the layer height and printhead speed are determinant parameters for the extent of successive layer fusion. Moreover, maintenance of an optimal bath temperature is identified as a key parameter for establishing the printability for the hydrogel bio-ink. Studying this effect is enabled by the custom design of a PID temperature control system with integration with the bioprinter for real-time precision control of the support bath temperature. In order to qualify the printed construct, a surface irregularity metric, defined as the average height difference between consecutive local maximum and minimum points of the binary image contour for the printed structure, is advanced to evaluate the quality of the printed constructs. Complex one-to-four bifurcating tubular structure prints demonstrate the applicability of the optimized bioprinting parameter space to create exemplar 3D human vessel-like structures. Finally, a cell viability assay and perfusion test for a printed cell-laden tubular element demonstrates high cell survival rates and leakage-free flow, respectively.
3D cell printing is an emerging technology for fabricating complex cell-laden constructs with precise and pre-designed geometry, structure and composition to overcome the limitations of 2D cell culture and conventional tissue engineering scaffold technology. This technology enables spatial manipulation of cells and biomaterials, also referred to as 'bioink', and thus allows study of cellular interactions in a 3D microenvironment and/or in the formation of functional tissues and organs. Recently, many efforts have been made to develop new bioinks and to apply more cell sources for better biocompatibility and biofunctionality. However, the influences of printing parameters on the shape fidelity of 3D constructs as well as on cell viability after the cell printing process have been poorly characterized. Furthermore, parameter optimization based on a specific cell type might not be suitable for other types of cells, especially cells with high sensibility. In this study, we systematically studied the influence of bioink properties and printing parameters on bioink printability and embryonic stem cell (ESC) viability in the process of extrusion-based cell printing, also known as bioplotting. A novel method was established to determine suitable conditions for bioplotting ESCs to achieve both good printability and high cell viability. The rheological properties of gelatin/alginate bioinks were evaluated to determine the gelation properties under different bioink compositions, printing temperatures and holding times. The bioink printability was characterized by a newly developed semi-quantitative method. The results demonstrated that bioinks with longer gelation times would result in poorer printability. The live/dead assay showed that ESC viability increased with higher printing temperatures and lower gelatin concentrations. Furthermore, an exponential relationship was obtained between ESC viability and induced shear stress. By defining the proper printability and acceptable viability ranges, a combined parameters region was obtained. This study provides guidance for parameter optimization and the fine-tuning of 3D cell printing processes regarding both bioink printability and cell viability after bioplotting, especially for easily damaged cells, like ESCs.
3D tissue printing with adult stem cells is reported. A novel cell-containing multicomponent bioink is used in a two-step 3D printing process to engineer bone and cartilage architectures.
Microcrystalline cellulose (MCC) was successfully prepared from bleached kenaf bast fiber through hydrochloric acid hydrolysis. The influence of hydrolysis time (1 to 3 h) on the MCC physicochemical properties was examined. Scanning electron microscopy (SEM), X-ray diffraction (XRD), particle size analysis, Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) were utilized to characterize the isolated MCC. According to FTIR analysis, the chemical composition of MCC was not changed with the reaction time. The reaction times, however, did affect the thermal stability of MCC. The thermal stability decreased linearly with increasing hydrolysis time. The optimum hydrolysis time was determined based on the morphological, structural, and thermal properties of the kenaf bast MCC.
In this communication, we developed a thermally stable, biocompatible, and colonically degradable hydrogel-based device [pectin-co-poly(MAA)] for oral delivery of 5-fluorouracil (5-FU) to treat colon cancer with minimal upper gastrointestinal invasion. Toward this end, ethylene glycol dimethacrylate (EGDMA) cross-linked hydrogels of pectin were synthesized. Methacrylic acid (MAA) was grafted to impart pH-responsive character, whereas benzoyl peroxide (BPO) was applied for simultaneous grafting and cross-linking polymerization. The hydrogels were characterized by Fourier transform infrared , thermogravimetric analysis, differential scanning calorimetry, and X-ray diffractometry. Scanning electron microscopic photographs were taken to analyze the surface morphology. Swelling behavior was analyzed to assess better performance of biodegradable hydrogels for optimized loading and release of the drug targeted to the colon. Gel fraction, swelling ratio, diffusion coefficient, drug loading, and cumulative release increased with an increase of pectin ratio and decreased with an increase of MAA and EGDMA ratio. Strategically, hydrogels with higher amounts of pectin were prepared for complete degradation in the colon. Our investigations indicate that pectin-co-poly(MAA) hydrogel is a suitable delivery system developed for oral delivery of the drug targeted to the colon.
The synthesis of a macro-initiator from cellulose in mixtures of zinc-based ionic liquid and polar solvents including deep eutectic solvent, dimethylformamide, acetone, and tetrahydrofuran (THF) was studied. The results of FTIR and NMR spectroscopies indicated that the cellulose-based macro-initiator can only be obtained in an inert ether solvent, THF. When the amounts of cellulose and zinc-based ionic liquid were fixed at 0.5 g and 18 mL, respectively, the degree of substitution of the cellulose-based macro-initiator obtained was increased from 11.0% to 17.4% as the reaction temperature was increased from room temperature to 40 degrees C, as calculated from TGA thermograms. When the amount of cellulose was cut in half, a degree of substitution of 27.5% was achieved due to lower viscosity and better homogeneity of the reaction medium. A green, new, and relatively cheap approach has been shown to be suitable for synthesizing a cellulose-based macro-initiator.
Bioprinting is an emerging technology in the field of tissue engineering as it allows the precise positioning of biologically relevant materials in 3D, which more resembles the native tissue in our body than current homogenous, bulk approaches. There is however a lack of materials to be used with this technology and materials such as the block copolymer Pluronic have good printing properties but do not allow long-term cell culture. Here we present an approach called nanostructuring to increase the biocompatibility of Pluronic gels at printable concentrations. By mixing acrylated with unmodified Pluronic F127 it was possible to maintain the excellent printing properties of Pluronic and to create stable gels via UV crosslinking. By subsequent elution of the unmodified Pluronic from the crosslinked network we were able to increase the cell viability of encapsulated chondrocytes at day 14 from 62% for a pure acrylated Pluronic hydrogel to 86% for a nanostructured hydrogel. The mixed Pluronic gels also showed good printability when cells where included in the bioink. The nanostructured gels were, with a compressive modulus of 1.42 kPa, mechanically weak, but we were able to increase the mechanical properties by the addition of methacrylated hyaluronic acid. Our nanostructuring approach enables Pluronic hydrogels to have the desired set of properties in all stages of the bioprinting process.
Carboxymethyl cellulose (CMC) is a cellulose derivative having water-soluble property, biodegradability, and biocompatibility. It has been used in various medical applications as forms of gel, film, membrane, or powder. In this study, composite CMC nonwovens were produced, by a wet-laid nonwoven process, to improve the wet strength of carboxymethyl cellulose nonwovens. Followed by preparing the CMC fibers from cotton fiber, the composite CMC nonwovens composed of CMC fibers and PE/PP bicomponent fibers were manufactured by using 85/15 % v/v of ethanol/water solution as a dispersion medium. Structural analyses of CMC fibers, such as XRD, TGA, FT-IR, and degree of substitution indicated that CMC fibers were successfully produced. The wet strength of CMC nonwoven was dramatically increased by blending with the PE/PP fibers without sacrificing the key properties for wound dressing materials such as liquid absorption, gel blocking and liquid retention. It is expected that the composite CMC nonwovens will be a good candidate for wound dressing materials for mild exudate condition.
The present work deals with the development of pectin-gelatin (PEGE) hydrogel membranes for wound dressing applications. The prepared hydrogels were characterized by FTIR spectroscopy, XRD spectroscopy, water vapor transmission rate (WVTR) test and tensile strength test. Morphology and thermal stability of the membranes were analyzed by Field emission scanning electron microscopy (FESEM) and thermogravimetric analysis (TGA). The swelling studies of the hydrogels were conducted in different pH buffer solutions (pH 1.4, 5.4, 7.4 and 9.4). FTIR spectra of the hydrogels indicated considerable lowering in usual –OH stretching vibration peak of pectin and gelatin, which suggests the development of probable intermolecular interactions between the two natural polymers. XRD study revealed the decrease in crystallinity of hydrogels as compared to parent pectin. The morphological analysis of the hydrogel revealed highly interconnected honeycomb type architecture with pore size ranging from 10 to 40 μm. It was found that increase in gelatin ratio significantly improves the porous nature of the membranes. TGA study showed the enhanced thermal stability of PEGE hydrogel as compared to reference pectin. Tensile strength (TS) and elongation at break (EB) was found to increase with gelatin content in the hydrogel membranes but further increase leads to decrease in TS and EB. The WVTR analysis of the membranes showed the moisture retentive properties indicating its possible use in moist wound care. The PEGE hydrogels were found to be cytocompatible with B16 melanoma cells.
Novel interactive and thermoresponsive interpenetrating polymer network (IPN) films, which are transparent, permeable to oxygen, and have the potential to be easily stripped from a wound bed, were synthesised using rapid photopolymerisation and crosslinking of DEAAm in the presence of chitosan. This study provides the first evaluation and optimisation of a UV-polymerised chitosan–PDEAAm IPN composite film for application in wound dressings. FTIR spectroscopy and DSC analysis were used to initially characterise the resulting films. Modulated differential scanning calorimetry results showed that the dressings exhibited lower critical solution temperatures in the desired range, while the samples were also observed to undergo temperature-dependent swelling behaviour. This thermosensitive property would potentially allow the dressings to be easily detachable, which would enable frequent dressing changes if desired without causing further injury to healing tissues. Furthermore, the water content values recorded are in the typical and desired ranges for commercial wound dressings.
The cytotoxicity and in vitro effects of six variously modified types of cellulose (OC--oxidized cellulose, NaOC--oxidized cellulose sodium salt, DAC--dialdehyde cellulose, CMC--carboxymethyl cellulose, MFC--microfibrilated cellulose, and MCC--microcrystalline cellulose) on the inflammatory response in macrophage-like THP-1 cells were examined, with special focus on their ability to influence gene expression and the production of TNF-α. The study provides evidence that DAC exerts a marked effect on the induction of TNF-α gene expression and its subsequent production in human macrophages. Thus, the use of DAC for anti-hemorrhagic or wound-healing therapy should be considered carefully with regard to its pro-inflammatory activity. On the contrary, MCC showed significant anti-inflammatory effects in the LPS-induced conditions, which might be beneficial for the treatment of non-healing chronic wounds, e.g., diabetic or venous ulcers.
In this study, oxiconazole nitrate (OXI)-loaded antifungal thermosensitive chitosan/carboxymethylcellulose/scleroglucan/montmorillonite (CHT/CMC/SGL/MMT) nanocomposite hydrogels were developed for onychomycosis treatment. The presence of 5% (w/w) MMT within hydrogel matrix increased the glass transition temperature of CHT/CMC/SGL material from 63.72 °C to 76.75 °C and the compressive stress value from 126.45 ± 8.83 kPa to 266.99 ± 6.60 kPa. For the use of hydrogel materials in the treatment of onychomycosis, antifungal OXI drug was loaded into the network of thermosensitive CHT/CMC/SGL and CHT/CMC/SGL/MMT hydrogels and the release of OXI from these materials was monitored spectrophotometrically. At the end of 420 min, for hydrogel systems containing 0, 1, 3 and 5 % (w/w) MMT, OXI release amounts were determined as 70.33 ± 1.74 %, 63.92 ± 0.31 %, 58.78 ± 1.45 % and 52.89 ± 0.21 %, respectively. This means that the drug release depends on the MMT amount within hydrogel matrix and can be controlled by changing the amount of clay mineral in hydrogel material. OXI-loaded new hydrogels showed high antifungal activity against Trichophyton mentagrophytes and Trichophyton rubrum dermatophytes. This study suggests that new antifungal thermosensitive CHT/CMC/SGL/MMT nanocomposite hydrogels could be promising materials for onychomycosis treatment.
In this study, agar/κ-carrageenan/montmorillonite (MMT) hydrogels were prepared to examine their usability as wound dressing materials and to see the effect of MMT amount on some properties of agar/κ-carrageenan hydrogel materials. Hydrogels were characterized by SEM-EDX, TEM and DSC analyses. By increasing the MMT content within hydrogel matrix from 0% to 5%, the decomposition temperature of the hydrogel material was increased from 256.6 °C to 262.1 °C. Swelling amount of hydrogels in d-glucose solution (2682%) was found to be much higher compared with other physiological solutions such as physiological saline solution (937%), synthetic urine solution (746%) and simulated wound fluid (563%). The release studies of analgesic lidocaine hydrochloride (LDC) and antibiotic chloramphenicol (CLP) drugs from hydrogel systems demonstrated that the release amount of LDC and CLP from hydrogels could be controlled by MMT amount within hydrogel matrix. The concentrations of drugs within hydrogel sample stored at 4 °C for 6 months did not exhibit a significant change. Hydrogel materials containing CLP exhibited good antibacterial activity against E. coli and S. aureus. Cytotoxicity test results indicated that hydrogels were biocompatible with MG-63 cells. The ultimate compressive stress of agar/κ-carrageenan hydrogel with LDC and CLP and agar/κ-carrageenan/MMT hydrogel including 5% MMT with LDC and CLP was measured as 38.30 kPa and 47.70 kPa, respectively. The experimental results revealed that prepared agar/κ-carrageenan and agar/κ-carrageenan/MMT hydrogels have great potential for wound care applications.
The development of thermosensitive smart hydrogels with suitable thermosensitivity is of great importance for various biomedical and pharmaceutical applications. In this study, thermosensitive chitosan/carboxymethylcellulose/scleroglucan/montmorillonite (CHT/CMC/SGL/MMT) nanocomposite hydrogels were prepared for biomedical and pharmaceutical usages and characterized by using rheology, FTIR, SEM, EDX, TEM, XRD, TGA and swelling measurements. Exfoliated distribution of MMT in the network structure of hydrogels proved by XRD and TEM analyses caused a decrease in the pore size of hydrogels. Phase transition temperature of thermosensitive hydrogels was determined precisely by rheological measurements. In the presence of 5% MMT within hydrogel matrix, the gelling temperature of Sample 9 exhibited a decrease from 32.0 °C to 25.3 °C. It was found from TGA that among the CHT/CMC/SGL/MMT hydrogel materials the hydrogel system containing 5% MMT showed the highest decomposition temperature (175 °C). Furthermore, all hydrogel materials exhibited non-Fickian swelling behavior in distilled water and basic medium. The addition of MMT into the hydrogel matrix caused a significant decrease in the swelling amount of thermosensitive hydrogels. The results of this study indicate that thermosensitive CHT/CMC/SGL/MMT hydrogel materials may have potential applications in drug delivery, wound dressing and tissue engineering.
Peritoneal adhesion is a general complication following pelvic and abdominal surgery, which may lead to chronic abdominal pain, bowel obstruction, organ injury, and female infertility. Biodegradable polymer membranes have been suggested as physical barriers to prevent peritoneum adhesion. In this work, a transglutaminase (TGase)-catalyzed crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30, 25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion membranes shown enhanced mechanical properties and improved biodegradability. Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in vitro cell culture study. Moreover, the anti-adhesion membrane with the proportion of 25/25/50 was implanted between the artificially defected cecum and peritoneal wall in rats and following by general observation, histological examination, and inflammatory factors assay. The results indicated that the anti-adhesion membrane can significantly prevent peritoneal adhesion with negligible immunogenicity. Therefore, the composite membrane crosslinked by TGase had satisfactory anti-adhesive effects with high biocompatibility and low antigenicity, which could be used as a preventive barrier for peritoneal adhesion.
Gas barrier films with water-vapor-permeability have exhibited broad application prospects in gas separation and dehumidification. Herein, multilayer films comprised of layered double hydroxides (LDH) nanosheets and carboxymethyl cellulose sodium (CMC) were fabricated via layer-by-layer assembly. The resulting (LDH/CMC)n films show excellent gas barrier properties, which are ascribed to the significantly increased pathway for gas permeation originating from the large aspect ratio and high orientation of two-dimensional LDH nanosheets. Unlike traditional gas barrier films with nonselective blocking effect for various gases (including water vapor), the (LDH/CMC)n films exhibit unusual moisture permselective property. The moisture-permeable property was related with the hygroscopicity of CMC and hydrophilicity of LDH, which can enrich the water molecules from the surroundings and aggrandize the osmotic pressure for water vapor, resulting in an uncommon improvement of water vapor transmission. It is interesting to find that the (LDH/CMC)n films exhibit enhanced gas (O2, CO2, CH4 and N2) barrier properties upon treatment in a humid environment, due to the formation of hydrogen bonds between the infiltrated water molecules and hydrophilic groups in CMC, thus padding the interstitial space of the CMC molecular chains and increasing the gas transmission path. The reduction of free volume and extension of the gas transmission path further enhance the gas barrier properties of (LDH/CMC)n films. Moreover, the (LDH/CMC)n films represent the water vapor permselective property in mixed gas (including O2, CO2, CH4, N2 and water vapor), while maintaining the barrier for other gases, which can be potentially applied in air dehydration and dehumidification of natural gas.
The emergence of 3D printing is expected to solve the present puzzle in the field of regenerative medicine. However, the appropriate bioink was lacking due to the rigorous requirement of high printability and biocompatibility, often contradictory. In this study, a novel thixotropic magnesium phosphate-based gel (TMP-BG) was prepared and explored its application in 3D printing. The stable gel could be synthesized by adjusting the ratio of ternary reactants (NaOH, Mg(OH)2, and H3PO4). Moreover, the structure, morphology, particle size and composition of TMP-BG were characterized. Furthermore, the rheological, thixotropic behaviors and degradation of TMP-BG were investigated. The printability of TMP-BG was tested by using the extrusion-based 3D printer. The biocompatibility of TMP-BG was evaluated in vitro. The composition of TMP-BG was MgNa3H(PO4)2 with nanometer and sub-micro scale, which was easily form a complex three-dimensional porous structure. Rheological results showed that the gel had notable shear thinning behavior and good thixotropy, which could provide the TMP-BG with injectability and formability simultaneously. In addition, the thixotropic mechanisms of TMP-BG were speculated to be a model of “house of card”. Finally, TMP-BG could be printed into large size and different complex three-dimensional structures. Results of the MG-63 cell viability and cell proliferation confirmed the biocompatible of TMG-BG. The present newly developed TMP-BG would be potential to be used as 3D printing bioink involving cell for future applications in regenerative medicine.
In this study, novel porous three-dimensional (3D) scaffolds from silk fibroin (SF) and functionalized (amidated and oxidized) citrus pectin (PEC) were developed for skin tissue engineering applications. Crosslinking was achieved by Schiff's reaction in borax presence as crosslinking coordinating agent and CaCl2 addition. After freeze-drying and methanol treatment, plasma treatment (10 W, 3 min) was applied to remove surface skin layer formed on scaffolds. 3D matrices had high porosity (83%) and interconnectivity with pore size about 120 µm that providing suitable microenvironment for cells. Modifications on PEC chain and crosslinking of scaffolds were verified by fourier-transform infrared spectroscopy (FTIR) analysis and spectrophotometric assay. Scaffolds showed low weight loss (21.3% in 40 days) and high water uptake ability in phosphate-buffered saline (800% in 24 h). Mechanical properties of 3D matrices satisfied the stability of scaffolds under compressive stress and supported adhesion, proliferation and penetration of fibroblast cells. Our results suggested that modified PEC-SF scaffolds would be proposed for use in tissue engineered skin dermal substitutes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.
Following skin wounding, the healing outcome can be; regeneration, repair with normal scar tissue, repair with hypertrophic scar tissue, or the formation of keloids. The role of chemical factors in wound healing has been extensively explored, and while there is evidence suggesting the role of mechanical forces, its influence is much less well defined. Here we provide a brief review on the recent progress of the role of mechanical force in skin wound healing by comparing laboratory mice, African spiny mice, fetal wound healing, and adult scar keloid formation. A comparison across different species may provide insight into key regulators. Interestingly, some findings suggest tension can induce an immune response, and this provides a new link between mechanical and chemical forces. Clinically, manipulating skin tension has been demonstrated to be effective for scar prevention and treatment, but not for tissue regeneration. Utilizing this knowledge, specialists may modulate regulatory factors and develop therapeutic strategies to reduce scar formation and promote regeneration.
Thermal analysis is a series of laboratory techniques that measure physical and chemical properties of materials as a function of temperature and time.Thermal analysis results provide insight into the structure and quality of both starting materials and finished products. The physical structure (amorphous, crystalline, semi-crystalline) of a material creates a set of physical properties, which in turn define end-use properties, such as texture and storage stability. Areas of application include quality assurance, product development, and research into new materials, formulations, and processing conditions.This chapter covers the principles, experimental conditions, common measurements, and applications of the two most frequently used thermal analysis techniques, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).Also covered is modulated temperature DSC (MDSC®).This chapter includes illustrated application of thermal analysis to a variety of food materials.
The water extract of Green Jelly leaves (GJL) obtained by crushing the leaves in water (1:40) was capable of forming a gel at room temperature. The composition of GJL consisted mainly of carbohydrate (∼70 w/w), protein (∼13% w/w) and minerals (∼6% w/w). The mineral portion consisted of mainly calcium (∼1.2% w/w), zinc (∼0.12% w/w) and magnesium (∼ 0.11% w/w). The isolated polysaccharide fraction (∼42.6% w/w) consisted of mainly galacturonic acid (∼35.8% w/w) and neutral sugars (∼6.8% w/w), with a weight-average molecular weight of ∼4.4 × 10⁵ g/mol. The results obtained by Fourier Transform Infra-Red (FTIR) showed that GJL polysaccharide fraction had a fairly similar FTIR fingerprint as the commercial low-methoxyl pectin (LMP). The degree of esterification of the polysaccharide changed drastically (from 97% to 10%) depending on the temperature used during the extraction process. The zeta potential of the extracted polysaccharide showed high negative charged as compared to the commercial LMP but close to sodium alginate. The study showed that the gelation was divalent cation-mediated and probably facilitated by the low degree of esterification which reduced steric hindrance from the methyl ester groups.
Pectins are natural complex heteropolysaccharides, composed of (1, 4)-linked α-D-galacturonic acid residues and variety of neutral sugars such as rhamnose, galactose, arabinose. It is second most abundant component of the cell wall of all land plants. It has wide applications in various fields due to its use as gelling, emulsifying or stabilizing agent and as well as its non-toxic, biocompatible and biodegradable nature. Considering these versatile properties this review sheds a light on the synthesis, modification, characterization and applications of pectin based polymers. Most of them are used in industries, pharmaceutics, nutraceutics, drug delivery, tissue engineering, food packaging and cosmetics. Properties of pectin can be improved and modified by forming derivatives, blends and composites.
Plant cell walls have a unique combination of strength and flexibility however, further investigations are required to understand how those properties arise from the assembly of the relevant biopolymers. Recent studies indicate that Ca²⁺-pectates can act as load-bearing components in cell walls. To investigate this proposed role of pectins, bioinspired wall models were synthesised based on bacterial cellulose containing pectin-calcium gels by varying the order of assembly of cellulose/pectin networks, pectin degree of methylesterification and calcium concentration. Hydrogels in which pectin-calcium assembly occurred prior to cellulose synthesis showed evidence for direct cellulose/pectin interactions from small-angle scattering (SAXS and SANS), had the densest networks and the lowest normal stress. The strength of the pectin-calcium gel affected cellulose structure, crystallinity and material properties. The results highlight the importance of the order of assembly on the properties of cellulose composite networks and support the role of pectin in the mechanics of cell walls.
Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine.
Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing because of the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer-reviewed literature and other publicly available sources such as the US FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic wounds (e.g., accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue-engineered substitutes, biomaterials-based biological dressings, biological and naturally derived dressings, medicated sutures, and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging physical approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care.
The present study delineates preparation, characterization and application of calcium alginate (CA)-carboxymethyl cellulose (CMC) beads for colon-specific oral drug delivery. Here, we exploited pH responsive swelling, mucoadhesivity and colonic microflora-catered biodegradability of the formulations for colon-specific drug delivery. The CA-CMC beads were prepared by ionic gelation method and its physicochemical characterization was done by SEM, XRD, EDAX, DSC and texture analyzer. The swelling and mucoadhesivity of the beads was found higher at the simulated colonic environment. Variation was more prominent in compositions with lower CMC concentrations. CA-CMC formulations degraded slowly in simulated colonic fluid, however the degradation rate increased drastically in the presence of colonic microflora. In vitro release study of anticancer drug 5-fluorouracil (5-FU) showed a release (>90%) in the presence of colonic enzymes. A critical analysis of drug release profile along with FRAP (fluorescence recovery after photobleaching) study revealed that the presence of CMC in the formulation retarded the release rate of 5-FU. 5-FU-loaded formulations were tested against colon adenocarcinoma cells (HT-29). Cytotoxicity data, nuclear condensation-fragmentation and apoptosis analysis (by flow cytometry) together confirmed the therapeutic potential of the CA-CMC formulations. In conclusion, CA-CMC beads can be used for colon-specific drug delivery.
The thermal degradation of pectin was investigated by simultaneous TGA-DSC/FTIR analysis and Hi-Res/modulated-TGA technique under nitrogen atmosphere. Pyrolytic degradation is a complex set of simultaneous and consecutive reactions related to: (i) dehydration at temperatures ≤100 °C; (ii) initial depolymerization by breaking the glycosidic linkages for temperature ≤210 °C, (iii) secondary degradation of the pectin units between 250 and 580 °C, and (iv) direct gasification of char residues at temperatures ≥600 °C. Three model-free-kinetics algorithms, Friedman (F), Kissinger–Akahira–Sunouse (KAS) and modulated TGA (MTGA), were used to predict the pyrolytic cracking kinetics. The results are discussed in terms of activation energy, the most probable mechanisms, and their relationship with the structure.
The effects of microcrystalline cellulose (MCC) fibre on the properties of recycled polypropylene (rPP) composites were investigated. A coupling agent, maleic anhydride grafted-polypropylene (MAPP) was used to improve the interfacial adhesion between the MCC fibres and rPP matrix. A series of rPP/MCC composites, with or without MAPP, were compounded with an extruder and then moulded with an injection moulding machine. It was found that without MAPP, an increase in MCC loadings caused degradation in the tensile strength of rPP composites. However, the impact strength was higher compared to that of neat rPP prior to its decrease caused by the increase in MCC loading. All mechanical properties showed improvement after MAPP was added, especially in tensile modulus. FESEM morphology also revealed better interfacial adhesion between the MCC fibres and the rPP matrix. Fracture analysis indicated that the ductile and quasi-brittle behaviours in both types of rPP/MCC composites (with or without MAPP) were affected by the concentration of fibres and the interfacial adhesion strength.
Wound healing is a complex and dynamic process that involves the mediation of many initiators effective during the healing process such as cytokines, macrophages and fibroblasts. In addition, the defence mechanism of the body undergoes a step-by-step but continuous process known as the wound healing cascade to ensure optimal healing. Thus, when designing a wound healing system or dressing, it is pivotal that key factors such as optimal gaseous exchange, a moist wound environment, prevention of microbial activity and absorption of exudates are considered. A variety of wound dressings are available, however, not all meet the specific requirements of an ideal wound healing system to consider every aspect within the wound healing cascade. Recent research has focussed on the development of smart polymeric materials. Combining biopolymers that are crucial for wound healing may provide opportunities to synthesise matrices that are inductive to cells and that stimulate and trigger target cell responses crucial to the wound healing process. This review therefore outlines the processes involved in skin regeneration, optimal management and care required for wound treatment. It also assimilates, explores and discusses wound healing drug-delivery systems and nanotechnologies utilised for enhanced wound healing applications. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci
Polyvinyl alcohol (PVA)/cellulose nanowhisker (CNW) nanocomposite hydrogels to be used for wound dressing were obtained by freezing-thawing technique and characterized by means of morphological, physical, thermal, mechanical, barrier and antimicrobial properties. First, cellulose nanowhiskers were obtained by the acid hydrolysis of commercial crystalline microcellulose (MCC) and characterized by its size, shape, morphological, structural and thermal properties. Then, PVA/CNW nanocomposites with several CNW contents (0, 1, 3, 5 and 7wt.%) were obtained. Morphological, thermal, chemical and physical characterization of the PVA/CNW nanocomposite hydrogels was carried out. It was found that the addition of CNW to the hydrogel allows controlling the pore morphology of the samples. On the other hand, the transparency of the samples was maintained, the thermal stability was increased, the mechanical properties were improved and the water vapor transmission rate was in the range of wound dressing applications after CNW incorporation inside the PVA hydrogel matrix. The evaluation of microbial penetration showed that the prepared hydrogels can be considered as a good barrier against different microorganisms. All obtained results indicate that the PVA/CNW materials are promising to be used as wound dressing.
Highly porous three-dimensional scaffolds made of biopolymers are of great interest in tissue engineering applications. A novel scaffold composed of pectin, carboxymethyl cellulose (CMC) and microfibrillated cellulose (MFC) were synthesised using lyophilisation technique. The optimised scaffold with 0.1% MFC, C(0.1%), showed highest compression modulus (∼3.987MPa) and glass transition temperature (∼103°C). The pore size for the control scaffold, C(0%), was in the range of 30-300μm while it was significantly reduced to 10-250μm in case of C(0.1%). Using micro computed tomography, the porosity of C(0.1%) was estimated to be 88%. C(0.1%) showed excellent thermal stability and lower degradation rate compared to C(0%). The prepared samples were also characterised using XRD and FTIR. C(0.1%) showed controlled water uptake ability and in vitro degradation in PBS. It exhibited highest cell viability on NIH3T3 fibroblast cell line. These results suggest that these biocompatible composite scaffolds can be used for tissue engineering applications.
Stable hollow microcapsules composed of sodium carboxymethyl cellulose (CMC) and poly (allylamine hydrochloride) (PAH) were produced by layer-by-layer adsorption of polyelectrolytes onto CaCO(3) microparticles. Subsequently the core was removed by addition of chelating agents for calcium ions. Zeta potential studies showed charge reversal with deposition of successive polyelectrolyte layers, indicating that the alternate electrostatic adsorption of polyelectrolytes of opposite charge was successfully achieved. The size and surface morphology of the capsules was characterized by various microscopy techniques. The pH responsive loading behavior was elucidated by confocal laser scanning microscopy (CLSM) studies using fluorescence labeled dextran (FITC-dextran) and labeled BSA (FITC-BSA). CLSM images confirmed the open (pH≤6) and closed state (pH≥7) of the capsules. A model drug bovine serum albumin (BSA) was spontaneously loaded below its isoelectric point into hollow microcapsules, where BSA is positively charged. The loading of the BSA into the microcapsules was found to be dependent on the feeding concentration and pH of the medium. 65% of the loaded BSA was released over 7h of which about 34% was released in the first hour. These findings demonstrate that (CMC/PAH)(2) hollow capsules can be further exploited as a potential drug delivery system.
Pectin, due to its simple and cytocompatible gelling mechanism, has been recently exploited for different biomedical applications including drug delivery, gene delivery, wound healing and tissue engineering. Recent studies involving pectin for the biomedical field are reviewed, with the aim to capture the state of art on current research about pectin gels for biomedical applications, moving outside the traditional fields of application such as the food industry or pharmaceutics. Pectin structure, sources and extraction procedures have been discussed focussing on the properties of the polysaccharide that can be tuned to optimize the gels for a desired application and possess a fundamental role in application of pectin in the biomedical field.
Pectin-high amylose starch mixtures (1:4; 1:1; 4:1) were cross-linked at different degrees and characterized by rheological, thermal, X-ray diffraction and NMR analyses. For comparison, samples without cross-linker addition were also prepared and characterized. Although all samples behaved as gels, the results evidenced that the phosphorylation reaction promotes the network strengthening, resulting in covalent gels (highest critical stress, G' and recovery %). Likewise, cross-linked samples presented the highest thermal stability. However, alkaline treatment without cross-linker allowed a structural reorganization of samples, as they also behaved as covalent gels, but weaker than those gels from cross-linked samples, and presented higher thermal stability than the physical mixtures. X-ray diffractograms also evidenced the occurrence of physical and chemical modifications due to the cross-linking process and indicated that samples without cross-linker underwent some structural reorganization, resulting in a decrease of crystallinity. The chemical shift of resonance signals corroborates the occurrence of structural modifications by both alkaline treatment and cross-linking reaction.
Combinations of microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (Na-CMC) are commonly used as stabilising agents and suspending agents in pharmaceutical formulations. This paper is based on a study of the interactions that take place during the process of hydrogel formation, break down, and recovery. Also considered is the binding that occurs between the MCC and the Na-CMC. Avicel RC 591, a processed mixture of MCC and Na-CMC, is one of the more commonly used commercial suspending agents for aqueous compositions. Avicel RC 591 is used as an effective, blended stabilising agent. In this study, the contributions made by each of the components of Avicel RC 591 have been rationalised by monitoring the behaviour of the individual components in Avicel RC 591 suspensions or solutions. The hydrogels that are formed by Avicel RC 591 and by their laboratory formulated equivalent, which is spray dried (MCC+Na-CMC), have been characterised by confocal microscopy scanning electron microscopy and by dynamic light scattering. A 3D network structure that is formed by the MCC, in Avicel RC 591 is visualised. This network is supported by hydrogen bonding and by ionic interactions among and between the MCC, the Na-CMC and water. The strength of the network determines the physical properties of the hydrogel system, as seen in the rheological behaviour.
This study investigated critical physicochemical attributes of low (LV), medium (MV) and high molecular weight (HV) sodium carboxymethylcellulose (SCMC) scaffolds in partial thickness wound healing. SCMC scaffolds were prepared by solvent-evaporation technique. Their in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution, and in vivo wound healing profiles were determined. Inferring from rat wound size, re-epithelialization and histological profiles, wound healing progressed with HV scaffold>LV-MV scaffold>control with no scaffold. The transepidermal water loss (TEWL) from wound of rats treated by control>HV scaffold>LV-MV scaffold. HV scaffold had the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low moisture affinity characteristics. The HV scaffold can protect moisture loss without its excessive accumulation at wound bed which hindered re-epithelialization process. Regulation of transepidermal water movement and wound healing by scaffolds was governed by SCMC molecular weight instead of its carboxymethyl substitution degree or matrix pore size distribution, with large molecular weight HV preferred over lower molecular weight samples.
Treatment of chronic leg ulcers remains a major health care issue. Although many reports have examined different topical dressings, none have specifically looked at microcrystalline cellulose (MCC). We aimed to evaluate in a prospective, open study the safety and performance of a MCC membrane (Veloderm) in a series of chronic leg wounds of different aetiology. Fifty-five patients participated in this study. The membrane was applied every 5-10 days for 1 month, immediately after surgical debridement. The wound bed was assessed on days 7, 15 and 30 for erythema, pain, exudate level and infection. The wound size change at 30 days was the primary efficacy parameter and any adverse events were collected and analysed. A wound size change of 55% was achieved at the end of follow-up, with an improvement in all the collected parameters, but the erythema, which showed a mild increase. To date, this is the largest experience with a MCC product in chronic wounds. Our study suggests that this treatment may be safe and useful and deserves further investigation.