Effect of Poly(Vinyl Pyrrolidone) on Iodine Release from Acrylate-Endcapped Urethane-Based Poly(Ethylene Glycol) Hydrogels as Antibacterial Wound Dressing.

Infections are still a major cause of morbidity in burn wounds. Although silver has been used strongly in past centuries as an anti-bacterial, it can lead to allergic reactions, bacterial resistance, and delayed wound healing. Iodine-based antibacterials are becoming an interesting alternative. In this work, the effect of complexation with poly(vinyl pyrrolidone) (PVP) and poly(ethylene oxide) (PEO)-based polymers is explored by using different acrylate-endcapped urethane-based poly(ethylene glycol) (AUP) polymers, varying the molar mass (MM) of the poly(ethylene glycol) (PEG) backbone, with possible addition of PVP. The higher MM AUP outperforms the swelling potential of commercial wound dressings such as Kaltostat, Aquacel Ag, and Hydrosorb and all MM show superior mechanical properties. The addition of iodine to the polymers is compared to Iso-Betadine Tulle (IBT). Interestingly, the addition of PVP does not lead to increased iodine complexation compared to the blank AUP polymers, while all have a prolonged iodine release compared to the IBT, which leads to a burst release. The observed prolonged release also leads to larger inhibition zones during antibacterial tests. Complexing iodine in AUP polymers with or without PVP leads to antimicrobial wound dressings which may hold potential for future application to treat infected wounds.

Electron-Beam-Initiated Crosslinking of Methacrylated Alginate and Diacrylated Poly(ethylene glycol) Hydrogels.

An ideal wound dressing not only needs to absorb excess exudate but should also allow for a moist wound-healing environment as well as being mechanically strong. Such a dressing can be achieved by combining both a natural (alginate) and synthetic (poly(ethylene glycol) polymer. Interestingly, using an electron beam on (meth)acrylated polymers allows their covalent crosslinking without the use of toxic photo-initiators. The goal of this work was to crosslink alginate at different methacrylation degrees (26.1 and 53.5% of the repeating units) with diacrylated poly(ethylene glycol) (PEGDA) using electron-beam irradiation at different doses to create strong, transparent hydrogels. Infrared spectroscopy showed that both polymers were homogeneously distributed within the irradiated hydrogel. Rheology showed that the addition of PEGDA into alginate with a high degree of methacrylation and a polymer concentration of 6 wt/v% improved the storage modulus up to 15,867 ± 1102 Pa. Gel fractions > 90% and swelling ratios ranging from 10 to 250 times its own weight were obtained. It was observed that the higher the storage modulus, the more limited the swelling ratio due to a more crosslinked network. Finally, all species were highly transparent, with transmittance values > 80%. This may be beneficial for the visual inspection of healing progression. Furthermore, these polymers may eventually be used as carriers of photosensitizers, which is favorable in applications such as photodynamic therapy.

Fine-Tuning the Endcap Chemistry of Acrylated Poly(Ethylene Glycol)-Based Hydrogels for Efficient Burn Wound Exudate Management.

Most commercial dressings with moderate to high exudate uptake capacities are mechanically weaker and/or require a secondary dressing. The current research article focuses on the development of hydrogel-based wound dressings combining mechanical strength with high exudate absorption capacities using acrylate-endcapped urethane-based precursors (AUPs). AUPs with varying poly(ethylene glycol) backbone molar masses (10 and 20 kg mol-1 ) and endcap chemistries are successfully synthesized in toluene, subsequently processed into UV-cured hydrogel sheets and are benchmarked against several commercial wound dressings (Hydrosorb, Kaltostat, and Mepilex Ag). The AUP materials show high gel fractions (>90%) together with strong swelling degrees in water, phosphate buffered saline and simulated wound fluid (12.7-19.6 g g-1 ), as well as tunable mechanical properties (e.g., Young's modulus: 0.026-0.061 MPa). The AUPs have significantly (p < 0.05) higher swelling degrees than the tested commercial dressings, while also being mechanically resistant. The elasticity of the synthesized materials leads to an increased resistance against fatigue. The di- and hexa-acrylated AUPs show excellent in vitro biocompatibility against human foreskin fibroblasts, as evidenced by indirect MTS assays and live/dead cell assays. In conclusion, the processed AUP materials demonstrate high potential for wound healing application and can even compete with commercially available dressings.

Commercial wound dressings for the treatment of exuding wounds: an in-depth physico-chemical comparative study.

Background: Nowadays, a wide range of wound dressings is already commercially available. The selection of the dressing is of paramount importance as inappropriate wound management and dressing selection can delay the wound healing process. Not only can this be distressing for the patient, but it can also contribute to complications such as maceration and subsequent infection. Many researchers are targeting the design of dressings with superior properties over existing commercial dressings. However, reported results in the state-of-the-art are rarely benchmarked against commercial dressings. The aim of this study was to determine several characteristics of a large variety of the most frequently used commercial wound dressings, providing an overview for both practitioners and researchers. Methods: For this comparative study, 11 frequently used commercial wound dressings were selected, representing the different types. The morphology was studied using scanning electron microscopy. The dressings were characterized in terms of swelling capacity (water, phosphate buffered saline and simulated wound fluid), moisture vapour transmission rate (MVTR) and moisture uptake capacity (via dynamic vapour sorption) as well as mechanical properties using tensile testing and texturometry. Results: The selected dressings showed distinctive morphological differences (fibrous, porous and/or gel) which was reflected in the different properties. Indeed, the swelling capacities ranged between 1.5 and 23.2 g/g (water), 2.1 and 17.6 g/g (phosphate buffered saline) or 2.9 and 20.8 g/g (simulated wound fluid). The swelling capacity of the dressings in water increased even further upon freeze-drying, due to the formation of pores. The MVTR values varied between 40 and 930 g/m2/24 h. The maximal moisture uptake capacity varied between 5.8% and 105.7% at 95% relative humidity. Some commercial dressings exhibited a superior mechanical strength, due to either being hydrophobic or multi-layered. Conclusions: The present work not only offers insight into a valuable toolbox of suitable wound dressing characterization techniques, but also provides an extensive landscaping of commercial dressings along with their physico-chemical properties, obtained through reproducible experimental protocols. Furthermore, it ensures appropriate benchmark values for commercial dressings in all forthcoming studies and could aid researchers with the development of novel modern wound dressings. The tested dressings either exhibited a high strength or a high swelling capacity, suggesting that there is still a strong potential in the wound dressings market for dressings that possess both.

Polymer-Based Constructs for Flexor Tendon Repair: A Review.

A flexor tendon injury is acquired fast and is common for athletes, construction workers, and military personnel among others, treated in the emergency department. However, the healing of injured flexor tendons is stretched over a long period of up to 12 weeks, therefore, remaining a significant clinical problem. Postoperative complications, arising after traditional tendon repair strategies, include adhesion and tendon scar tissue formation, insufficient mechanical strength for early active mobilization, and infections. Various researchers have tried to develop innovative strategies for developing a polymer-based construct that minimalizes these postoperative complications, yet none are routinely used in clinical practice. Understanding the role such constructs play in tendon repair should enable a more targeted approach. This review mainly describes the polymer-based constructs that show promising results in solving these complications, in the hope that one day these will be used as a routine practice in flexor tendon repair, increasing the well-being of the patients. In addition, the review also focuses on the incorporation of active compounds in these constructs, to provide an enhanced healing environment for the flexor tendon.

Flexor tendon repair using a reinforced tubular, medicated electrospun construct.

A reinforced tubular, medicated electrospun construct was developed for deep flexor tendon repair. This construct combines mechanical strength with the release of anti-inflammatory and anti-adhesion drugs. In this study, the reinforced construct was evaluated using a rabbit model. It was compared to its components (a tubular, medicated electrospun polymer without reinforcement and a tubular braid as such) on the one hand to a modified Kessler suture as a control group. Forty New Zealand rabbits were randomly divided into two groups. Surgery was performed in the second and fourth deep flexor tendons of one hind paw of the rabbits in the two groups using four repair techniques. Biomechanical tensile testing and macroscopic and histological evaluations were performed at 3 and 8 weeks postoperatively. A two-way analysis of variance with pairwise comparisons revealed that the three experimental surgical techniques (a reinforced tubular medicated electrospun construct, tubular-medicated construct, and tubular braid as such) showed similar strength as that of a modified Kessler suture repair, which was characterized by a mean load at ultimate failure of 19.85 N (standard deviation [SD] 5.29 N) at 3 weeks and 18.15 N (SD 8.01 N) at 8 weeks. Macroscopically, a significantly different adhesion pattern was observed at the suture knots, either centrally or peripherally, depending on the technique. Histologically, a qualitative assessment showed good to excellent repair at the tendon repair site, irrespective of the applied technique. This study demonstrates that mechanical and biological repair strategies for flexor tendon repair can be successfully combined.

Design, preparation and in vitro characterization of biomimetic and bioactive chitosan/polyethylene oxide based nanofibers as wound dressings.

Chitosan-based nanofibers (CS-NFs) are excellent artificial extracellular matrices (ECMs) due to the resemblance of CS with the glycosaminoglycans of the natural ECMs. Despite this excellent feature, the poor electrospinnability and mechanical properties of CS are responsible for important limitations in respect to its biomedical applications. To improve the CS's physico-chemical properties, new bioactive and biomimetic CS-NFs were formulated with polyethylene oxide (PEO), having incorporated different active components (ACs) with important beneficial effects for healing. Manuka honey (trophic and antimicrobial effects), propolis (antimicrobial effects), Calendula officinalis infusion (antioxidant effect, reepithelialization stimulating agent), insulin (trophic effect), and L-arginine (angiogenic effect) were selected as ACs. SEM morphology analysis revealed well-alignment, unidirectional arrays, with small diameters, no beads, and smooth surfaces for developed CS_PEO-ACs NFs. The developed NFs showed good biodegradability (NFs mats lost up to 60% of their initial weight in PBS), increased hemocompatibility (hemolytic index less than 4%), and a reduced cytotoxicity degree (cell viability degree more than 90%). In addition, significant antioxidant and antimicrobial effects were noted for the developed NFs which make them suitable for chronic wounds, due to the role of oxidative stress and infection risk in delaying normal wound healing. The most suitable for wound healing applications seems to be CS_PEO@P_C which showed an improved hemolysis index (2.92 ± 0.16%), is non-toxic (cell viability degree more than 97%), and has also significant radical scavenging effect (DPPH inhibition more than 65%). In addition, CS_PEO@P_C presents increased antimicrobial effects, more noticeably for Staphylococcus aureus strain, which is a key feature in preventing wound infection and delaying the healing process. It can be concluded that the developed CS/PEO-ACs NFs are very promising biomaterials for wound care, especially CS_PEO@P_C.

Acrylate-endcapped urethane-based hydrogels: An in vivo study on wound healing potential.

Improving wound healing by developing innovative dressing materials has been an important focus over the past few years in the biomedical field. In this regard, the current study focuses on developing new dressings based on acrylate-endcapped urethane-based polymers (AUPs). The materials have been processed into films and electrospun mats. Exudate uptake capacity, mechanical properties and fiber morphology were evaluated herein. The results showed superior uptake capacity of both films and mats when compared to Aquacel®Ag, Exufiber® and Help®. Addition of a high molar mass poly(ethylene glycol) to the AUP polymers benefits both the film and electrospun dressings in terms of flexibility and elongation. An in vivo study was conducted to assess the wound healing properties of these dressings on an acute wound model induced to rats. A macroscopic evaluation indicated that wound contraction and wound fraction percentages were improved significantly in case of the AUP-materials when compared to both the positive (Aquacel®Ag) and negative (Exufiber® and Help®) controls. A histopathological assay, to underline the changes noticed on a macroscopical level, was also performed. The data obtained proved that the developed dressings are beneficial towards tissue regeneration and accelerated wound healing. These findings offer a practical yet adequate strategy for the fabrication of acrylate-endcapped urethane-based materials for wound healing applications.

Photo-Crosslinked Gelatin-Based Hydrogel Films to Support Wound Healing.

Gelatin is used widely in the biomedical field, among other for wound healing. Given its upper critical solution temperature, crosslinking is required. To this end, gelatin is chemically modified with different photo-crosslinkable moieties with low (32-34%) and high (63-65%) degree of substitution (DS): gelatin-methacrylamide (gel-MA) and gelatin-acrylamide (gel-AA) and gelatin-pentenamide (gel-PE). Next to the more researched gel-MA, it is especially interesting and novel to compare with other gelatin-derived compounds for the application of wound healing. An additional comparison is made with commercial dressings. The DS is directly proportional to the mechanical characteristics and inversely proportional to the swelling capacity. Gel-PE shows weaker mechanical properties (G' < 15 kPa) than gel-AA and gel-MA (G' < 39 and 45 kPa, respectively). All derivatives are predominantly elastic (recovery indices of 89-94%). Gel-AA and gel-MA show excellent biocompatibility, whereas gel-PE shows a significantly lower initial biocompatibility, evolving positively toward day 7. Overall, gel-MA shows to have the most potential to be applied as wound dressing. Future blending with gel-AA to improve the curing kinetics can lead to dressings able to compete with current commercial dressings.

Gelatin-Based Versus Alginate-Based Hydrogels: Providing Insight in Wound Healing Potential.

Wound dressings under the form of films constituted of modified alginate (methacrylated alginate - AlgMA) versus a gelatine derivative containing norbornene functionalities (GelNB) are developed and evaluated for their moisturizing effects, followed by further in vivo testing to assay their wound healing potential. The gel fraction results shows that AlgMA and GelNB films displayed a high crosslinking efficiency while the swelling assay reveals a stronger water uptake capacity for AlgMA films compared to GelNB and to commercial dressing AquacelAg, used as positive control. Referring to the in vivo wound healing effect, the GelNB films not only exhibit proper healing properties, yet is higher to the AquacelAg, while the AlgMA films exhibit similar wound healing effect as the positive control. On a microscopic level, the healing phases (from inflammation to proliferation and contraction) are present for both materials, yet at a faster rate for the GelNB films, which is in line with the macroscopic findings. These results provide data which support that GelNB films outperform AlgMA films, but both can be used for wound healing applications.

New Hyaluronic Acid/Polyethylene Oxide-Based Electrospun Nanofibers: Design, Characterization and In Vitro Biological Evaluation.

Natural compounds have been used as wound-healing promoters and are also present in today's clinical proceedings. In this research, different natural active components such as propolis, Manuka honey, insulin, L-arginine, and Calendula officinalis infusion were included into hyaluronic acid/poly(ethylene)oxide-based electrospun nanofiber membranes to design innovative wound-dressing biomaterials. Morphology and average fiber diameter were analyzed by scanning electron microscopy. Chemical composition was proved by Fourier transform infrared spectroscopy, which indicated successful incorporation of the active components. The nanofiber membranes with propolis and Calendula officinalis showed best antioxidant activity, cytocompatibility, and antimicrobial properties against pathogen strains Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa and had an average diameter of 217 ± 19 nm with smooth surface aspect. Water vapor transmission rate was in agreement with the range suitable for preventing infections or wound dehydration (~5000 g/m2 24 h). Therefore, the developed hyaluronic acid/poly(ethylene)oxide nanofibers with additional natural components showed favorable features for clinical use as wound dressings.

Synthetic, Natural, and Semisynthetic Polymer Carriers for Controlled Nitric Oxide Release in Dermal Applications: A Review.

Nitric oxide (NO•) is a free radical gas, produced in the human body to regulate physiological processes, such as inflammatory and immune responses. It is required for skin health; therefore, a lack of NO• is known to cause or worsen skin conditions related to three biomedical applications- infection treatment, injury healing, and blood circulation. Therefore, research on its topical release has been increasing for the last two decades. The storage and delivery of nitric oxide in physiological conditions to compensate for its deficiency is achieved through pharmacological compounds called NO-donors. These are further incorporated into scaffolds to enhance therapeutic treatment. A wide range of polymeric scaffolds has been developed and tested for this purpose. Hence, this review aims to give a detailed overview of the natural, synthetic, and semisynthetic polymeric matrices that have been evaluated for antimicrobial, wound healing, and circulatory dermal applications. These matrices have already set a solid foundation in nitric oxide release and their future perspective is headed toward an enhanced controlled release by novel functionalized semisynthetic polymer carriers and co-delivery synergetic platforms. Finally, further clinical tests on patients with the targeted condition will hopefully enable the eventual commercialization of these systems.

Design and development of a reinforced tubular electrospun construct for the repair of ruptures of deep flexor tendons.

This research aims at developing a more potent solution for deep flexor tendon repair by combining a mechanical and biological approach. A reinforced, multi-layered electrospun tubular construct is developed, composed of three layers: an inner electrospun layer containing an anti-inflammatory component (Naproxen), a middle layer of braided monofilament as reinforcement and an outer electrospun layer containing an anti-adhesion component (hyaluronic acid, HA). In a first step, a novel acrylate endcapped urethane-based precursor (AUP) is developed and characterized by measuring molar mass, acrylate content and thermo-stability. The AUP material is benchmarked against commercially available poly(ε-caprolactone) (PCL). Next, the materials are processed into multi-layered, tubular constructs with bio-active components (Naproxen and HA) using electrospinning. In vitro assays using human fibroblasts show that incorporation of the bio-active components is successful and not-cytotoxic. Moreover, tensile testing using ex vivo sheep tendons prove that the developed multi-layered constructs fulfill the required strength for tendon repair (i.e. 2.79-3.98 MPa), with an ultimate strength of 8.56 ±â€¯1.92 MPa and 8.36 ±â€¯0.57 MPa for PCL and AUP/PCL constructs respectively. In conclusion, by combining a mechanical approach (improved mechanical properties) with the incorporation of bio-active compounds (biological approach), this solution shows its potential for application in deep flexor tendon repair.

Deformations in Cement Pastes during Capillary Imbibition and Their Relation to Water and Isopropanol as Imbibing Liquids.

The traditional approach for evaluating capillary imbibition, which describes the phenomena as a linear relationship between mass gain and the square root of time, considers a rigid pore structure. The common deviation from the linearity when using the square-root law (manifested in a downward curvature, i.e., slower water ingress) can be explained by considering a changing pore structure during the process caused by the swelling of calcium silicate hydrate (C-S-H) during water ingress. Analysing how the combination of deforming phase (C-S-H), non-deforming phase, and porosity affects the capillary water ingress rate is relevant for a deeper understanding of concrete durability. In this research, the C-S-H content was quantified by means of XRD diffraction coupled with Rietveld + PONKCS, dynamic water sorption (DVS), and SEM/BSE images coupled with phase mapping using PhAse Recognition and Characterization (PARC) software. The porosity was assessed by mercury intrusion porosimetry, water absorption under vacuum, and DVS. Furthermore, to assess deformations occurring with water and a non-aqueous imbibant, capillary imbibition tests with water and isopropanol as invading liquids were performed along with simultaneous deformation measurements. The relation between the relative C-S-H content and porosity has a great impact on the transport process. Samples exposed to isopropanol presented a much larger liquid uptake but significantly fewer deformations in comparison to imbibition with water. The effects of the changing pore structure were also evaluated with the Thomas and Jennings model, from which calculations indicated that pore shrink during imbibition. A comprehensive description of the relation between deformations and capillary imbibition in cement pastes reveals that liquid ingress is highly influenced by deformations.

Development of Gelatin-Alginate Hydrogels for Burn Wound Treatment.

Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel-MA/alg-MA). In one protocol gel-MA films are incubated in alg-MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(-MA) to gel-MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin-alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth.

Crack Mitigation in Concrete: Superabsorbent Polymers as Key to Success?

Cracking is a major concern in building applications. Cracks may arise from shrinkage, freeze/thawing and/or structural stresses, amongst others. Several solutions can be found but superabsorbent polymers (SAPs) seem to be interesting to counteract these problems. At an early age, the absorbed water by the SAPs may be used to mitigate autogenous and plastic shrinkage. The formed macro pores may increase the freeze/thaw resistance. The swelling upon water ingress may seal a crack from intruding fluids and may regain the overall water-tightness. The latter water may promote autogenous healing. The use of superabsorbent polymers is thus very interesting. This review paper summarizes the current research and gives a critical note towards the use of superabsorbent polymers in cementitious materials.

Characterization of methacrylated polysaccharides in combination with amine-based monomers for application in mortar.

Smart pH-responsive superabsorbent polymers (SAPs) could be useful for self-healing of cracks in mortar. They will swell minimally during the alkaline conditions of mixing, leading to only small macro-pores but will swell stronger with a lower pH when water enters the cracks. As such, polysaccharides (alginate, chitosan and agarose) were methacrylated and cross-linked with amine-based monomers (dimethylaminoethyl methacrylate and dimethylaminopropyl methacrylamide) to induce a varying pH-sensitivity. These materials showed a strong cross-linking efficiency and induced moisture uptake capacities up to 122% at 95% relative humidity with a negligible hysteresis. Additionally, interesting pH-responsive swelling capacities were obtained, especially for SAPs based on chitosan and agarose with values up to 110gwater/gSAP. Most of these materials showed limited hydrolysis in cement filtrate solutions, making them very promising for use in mortar.

Characterization of methacrylated alginate and acrylic monomers as versatile SAPs.

Superabsorbent polymers (SAPs) based on polysaccharides, especially alginate, could offer a valuable solution in a plethora of applications going from drug delivery to self-healing concrete. This has already been proven with both calcium alginate and methacrylated alginate combined with acrylic acid. In this manuscript, the effect of varying the degree of methacrylation and use of a combination of acrylic acid and acrylamide is investigated to explore the effects on the relevant SAP characteristics. The materials showed high gel fractions and a strong swelling capacity up to 630gwater/gSAP, especially for superabsorbent polymers with a low degree of substitution. The SAPs also showed only a limited hydrolysis in aqueous and cement filtrate solutions.

Alginate- and gelatin-based bioactive photocross-linkable hybrid materials for bone tissue engineering.

The paper presents the synthesis, the physico-chemical and the biological properties of novel hybrid materials prepared from photo-crosslinked gelatin/alginate-based hydrogels and silica particles exhibiting potential for the regeneration of bone tissue. Both alginate and gelatin were functionalized with methacrylate and methacrylamide moieties, respectively to render them photo-crosslinkable. Submicron silica particles of two sizes were dispersed within three types of polymeric sols including alginate, gelatin, and gelatin/alginate blends, which were subsequently photo-crosslinked. The swelling ratio, the gel fraction and the mechanical properties of the hybrid materials developed were examined and compared to these determined for reference hydrogel matrices. The in vitro cell culture studies have shown that the prepared materials exhibited biocompatibility as they supported both MEFs and MG-63 mitochondrial activity. Finally, the in vitro experiments performed under simulated body fluid conditions have revealed that due to inclusion of silica particles into the biopolymeric hydrogel matrices the mineralization was successfully induced.

Combinatory approach of methacrylated alginate and acid monomers for concrete applications.

Polysaccharides, and especially alginate, can be useful for self-healing of cracks in concrete. Instead of weak electrostatic bonds present within calcium alginate, covalent bonds, by methacrylation of the polysaccharides, will result in mechanically stronger superabsorbent polymers (SAPs). These methacrylated alginate chains as backbone are combined with two acrylic monomers in a varying molar fraction. These SAPs show a moisture uptake capacity up to 110% their own weight at a relative humidity of 95%, with a negligible hysteresis. The swelling capacity increased (up to 246 times its own weight) with a decreasing acrylic acid/2 acrylamido-2-methylpropane sulfonic acid ratio. The SAPs also showed a thermal stability up to 200°C. Interestingly, the SAP composed of alginate and acrylic acid exerted a very limited decrease in compressive strength (up to 7% with addition of 1wt% SAP) rendering this material interesting for the envisaged self-healing application.