Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties. Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks. At a higher concentration, CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by small-amplitude oscillatory shear rheological measurements and compression tests at different CXG/PA-H3 ratios. A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model

Xyloglucan-based hydrogels: A biomaterials chemistry contribution towards advanced wound healing

The last two decades have witnessed the introduction of several new wound dressings, with many of them being hydrogels for the advantages that these materials can offer in the application. However, despite the advancements and the wide range of dressings available, wound management is still an extremely challenging task due to its subjectivity, complexity and scarce knowledge of the wound healing process itself, and patient variability. For this reason, an interdisciplinary approach to wound care that can help reducing the incidence and prevalence of wounds is needed. One important goal would be to develop “smart” wound dressings that are easy to apply, wear and be removed, that are able to maintain a good balance between hydration of the wound bed and fluid absorption, that can act as a barrier against bacteria to prevent infections, yet allowing oxygenation, that are able to provide the physician with relevant information on physico-chemical and biological parameters to monitor the state of the wound and the healing process without requiring direct inspection, that can (eventually) release drugs or play regeneration functions to sustain and enhance the healing process. This very ambitious goal can only be achieved by merging contributions from different fields of research and expertise. In particular, the field of (bio)materials science and technology for the development of materials with the required combination of physico-chemical, mechanical and barrier properties, skin electronics for the integration of sensors and actuators, and tissue engineering to explore the possibility of including in the “smart” dressing also tissue regeneration function. The design of new materials for wound management applications can, in principle, benefit from the use of an intrinsically active polymer. Among all the available polymers, xyloglucan (XG) combines several favourable properties, which make it a suitable candidate for the scope: • It is abundant in nature, thus low-cost and its extraction is easy and high yield, • it is characterized by a very interesting self-assembly behaviour, • it is biodegradable and biocompatible; due to its vegetal origin it should not elicit the response of the human immune system, • there are a few studies concerning the possibility to employ this polysaccharide for biomedical applications, and it has been shown to have intrinsic activity such as anti-inflammatory properties for application through the skin and potential beneficial effect in reepithelization and remodelling, • it has film-forming properties, • and it is approved by FDA as food additive. For all of these reasons, xyloglucan is believed to have great potential on wound healing, making its application worth to be investigated. This study intends to attempt the merge of some elements from (bio)materials science, skin electronics and tissue engineering for the production of dressings and materials which could stimulate wound healing. In particular, it is aimed to: • develop a new platform of materials using xyloglucan to produce hydrogel as wound dressings and/or scaffolds; • investigate co-assembly as method to produce fibrous scaffolds that are known to favour wound healing; • identify a suitable technology that can allow the development of a wearable sensor for advanced wound management

Radiation synthesis of nanogels as therapeutic agent vectors

Nanogels (NGs) are physically or chemically crosslinked polymer networks and are promising candidates in the development of therapeutic agent vectors. In fact, thanks to their tunable size and properties, they offer unique advantages, including a large and flexible surface for multivalent bio-conjugation, an internal 3D aqueous environment for incorporation and protection of (bio)molecular drugs, stimuliresponsiveness to achieve temporal and/or site control of the release function and biocompatibility. In order to develop effective NGs-based biomedical devices an inexpensive, robust and versatile synthetic methodology is required. In this perspective, we have produced NGs with high yields and through-puts by pulsed electron-beam irradiation. In particular, using an industrial electron accelerator, carboxyl functionalized NGs from a dilute aqueous solutions of poly(N-vinyl pyrrolidone) (PVP), and acrylic acid as functional monomer have been produced. This process allows simultaneous polymer cross-linking and monomer grafting. Moreover, depending on the value of the total irradiation dose, also the sterilization of the irradiated material can be obtained. Since organic solvents, toxic initiators or catalysts and surfactants are not required, this procedure can be defined as an eco-friendly and clean one. Crosslinked nanoparticles with multi-armed surfaces, and size, crosslinking density, and surface electric charge density controlled, have been generated. Nanogels produced have been proven to be hemocompatible and not cytotoxic or genotoxic at the cellular level. NGs have been decorated with fluorescent probes, proteins and anti-MiR. Thanks to the use of fluorescent variants, it has been argued that NGs showed a good affinity for cells, as they rapidly and quantitatively bypass the cellular compartments, accumulating in specific cell portions for the first hours, and being completely released from the cells in the next 24 hours. Moreover, it has been proven that the proteins and anti-MiR, once conjugated, maintain their biological activity giving rise to targeting features toward specific cell types

Xyloglucan-based hydrogel films for the design of "smart" bandages

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do. Chronic wounds mostly affect people over the age of 60, but a significant proportion is becoming radiation induced chronic wounds caused by cancer radiotherapy. Hydrogels are often used as dressings in the management of a variety of wounds. These materials can help to maintain a moist wound environment, promote natural debridement, hydrate necrotic tissue, absorb slough and exudates.We are developing hydrogel dressings that can enable constant monitoring of selected key parameters through embedded radio-sensors, providing information on the progress of the reparative process, while maintaining the wound hydrated and oxygenated.Xyloglucan (XG) has been chosen asmain component of the hydrogel wound dressings. Chemical crosslinking has been induced to improve the mechanical properties of the films and prevent erosion. The effect of glycerol, used as plasticizer, on the structural and mechanical properties of the hydrogels has been investigated.Selected films resulted easy to handle, flexible and conformable, able to absorb high amounts of simulated biological fluids. Film biocompatibility and hemocompatibility was demonstrated by biological tests in which no injurious response was activated. Furthermore, we found that epithelial cells can partially adhere to the film whose ability to inhibit microorganisms growth and invasion was also demonstrated. The best candidate is now being integrated with a RFID radio-sensor to monitor the amount of exudates

Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application

Crosslinked xyloglucan-poly(vinyl alcohol) based hydrogel films are interesting materials for wound healing applications. This work focuses on the hydrolytic degradation and consequent morphological modification of a XG-PVA film and on its interaction with cells, blood, bacteria. Biocompatibility of the film was assessed in vitro by investigating different aspects, such as cell viability, oxidative stress level, mitochondrial dysfunction and specific stress biomarkers. Partial adhesiveness was demonstrated by performing different attaching assays and phalloidin staining. Hemocompatibility of XG-PVA film after interaction with blood was evaluated by using a multi-parametric approach, including human Red Blood Cells (RBC) count, hemolytic response and platelets activation. Thrombin and fibrinogen concentrations were examined as marker of the coagulation cascade. After direct contact with human blood and peripheral blood mononuclear cells (PBMC), no evidence of cell defense response was observed. Antimicrobial activity of XG-PVA film was tested against Escherichia coli (E.coli). XG-PVA film promotes bacterial retentivity and provides mechanical protection against bacterial infiltration. After loading the film with ampicillin, an inhibitory E. coli growth zone was observed. All together these results indicate that the XG-PVA system is a promising material to be tested in vivo for wound healing applications

Data concerning the protein absorption and retention properties of xyloglucan-based hydrogel film

In wound dressing applications, exudate absorption and retention are important properties. The data presented here assess the ability of the crosslinked xyloglucan-poly(vinyl alcohol) hydrogel films (XG-PVA), described in “Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships” (Ajovalasit et al., 2018) [1] and “Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application” (Picone et al., 2019), to absorb and retain proteins. These properties were investigated by Comassie blue staining and electrophoresis of Fetal Serum Proteins

Xyloglucan-based hydrogel films for wound dressing: Structure-property relationships

Thin xyloglucan-based hydrogel films have been synthetized and characterized in the prospect of producing wound dressings. Polyvinyl alcohol (PVA) and glycerol (Gro) were added to have an optimal combination of softness, conformability and resilience. Physical hydrogels have been transformed into permanent covalent hydrogels by reaction with glutaraldehyde (GA). Network structure-process-property relationships are discussed on the account of the results of several complementary characterizations: FTIR, rheology, thermal analysis, morphological analysis, moisture retention and swelling measurements. Selected formulations were also subjected to preliminary in vitro cytotoxicity tests. The physical and mechanical properties of some of the xyloglucan-based hydrogel films produced, combined with absence of cytotoxicity, make them suitable candidates for integration with sensors to monitor the wound healing process and further biological investigations in animal models