Intracellular reactive oxygen species (ROS) activity in hBMSCs measured from fluorescence emission at different times after treatment with VHC films extracts collected at 24 h. The diagrams include the mean, the standard deviation (n = 4) and the analysis of variance (ANOVA) between the different groups and the positive control at each time (* p < 0.05, ** p < 0.01, *** p < 0.001). 

Intracellular reactive oxygen species (ROS) activity in hBMSCs measured from fluorescence emission at different times after treatment with VHC films extracts collected at 24 h. The diagrams include the mean, the standard deviation (n = 4) and the analysis of variance (ANOVA) between the different groups and the positive control at each time (* p < 0.05, ** p < 0.01, *** p < 0.001). 

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The effective treatment of chronic wounds constitutes one of the most common worldwide healthcare problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system, avoiding tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable mem...

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... terpolymer systems efficiently reduced intracelular ROS production in vitro even when hBMSCs had been treated with H 2 O 2 activating the oxidative reaction (Figure 8). ROS production significantly decreased with respect to H 2 O 2 treated cells at any time, this reduction being more marked at shorter times. ...
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... production significantly decreased with respect to H 2 O 2 treated cells at any time, this reduction being more marked at shorter times. Furthermore, significant differences between the negative control (PBS) and VHC2 and VHC22 samples without H 2 O 2 separately, were not found (statistical data are not included in Figure 8 for simplification purposes). ...
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... terpolymer systems efficiently reduced intracelular ROS production in vitro even when hBMSCs had been treated with H2O2 activating the oxidative reaction (Figure 8). ROS production significantly decreased with respect to H2O2 treated cells at any time, this reduction being more marked at shorter times. ...
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... production significantly decreased with respect to H2O2 treated cells at any time, this reduction being more marked at shorter times. Furthermore, significant differences between the negative control (PBS) and VHC2 and VHC22 samples without H2O2 separately, were not found (statistical data are not included in Figure 8 for simplification purposes). Figure 8. Intracellular reactive oxygen species (ROS) activity in hBMSCs measured from fluorescence emission at different times after treatment with VHC films extracts collected at 24 h. ...
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... significant differences between the negative control (PBS) and VHC2 and VHC22 samples without H2O2 separately, were not found (statistical data are not included in Figure 8 for simplification purposes). Figure 8. Intracellular reactive oxygen species (ROS) activity in hBMSCs measured from fluorescence emission at different times after treatment with VHC films extracts collected at 24 h. ...
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... this way, we can analyze the direct response of the cells growing on the film and being in contact with the medium released, simulating the wound-regeneration process. After LPS stimulation for 24 h, the inhibitory effects of the terpolymers on the treated macrophages were observed (Figure 8). Cell viability was also taken into consideration, eliminating the possibility that the reduction of NO is due to cytotoxicity. ...

Citations

... Inspired by nature, polymeric tissue adhesives created by conjugating phenolic moieties (i.e., phenol, catechol, and gallol groups) to polymers have been extensively developed for various biomedical applications [28,[37][38][39][40]. The conjugation of catechol or gallol moieties to polymeric backbones provides beneficial functionalities along with strong tissue adhesiveness [28,[37][38][39][40]. ...
... Inspired by nature, polymeric tissue adhesives created by conjugating phenolic moieties (i.e., phenol, catechol, and gallol groups) to polymers have been extensively developed for various biomedical applications [28,[37][38][39][40]. The conjugation of catechol or gallol moieties to polymeric backbones provides beneficial functionalities along with strong tissue adhesiveness [28,[37][38][39][40]. For instance, catechol-conjugated chitosan (Chi-catechol), one of the mussel-inspired polymers, shows enhanced solubility in aqueous solution owing to the solubility of catechol moieties and hydrodynamic diameter changes [40]. ...
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The occurrence of leakage from anastomotic sites is a significant issue given its potential undesirable complications. The management of anastomotic leakage after gastrointestinal surgery is particularly crucial because it is directly associated with mortality and morbidity in patients. If adhesive materials could be used to support suturing in surgical procedures, many complications caused by leakage from the anastomosis sites could be prevented. In this study, we have developed self-healing, shear-thinning, tissue-adhesive, carbon-black-containing, gallic acid-conjugated chitosan (CB/Chi-gallol) hydrogels as sealing materials to be used with suturing. The addition of CB into Chi-gallol solution resulted in the formation of a crosslinked hydrogel with instantaneous solidification. In addition, these CB/Chi-gallol hydrogels showed enhancement of the elastic modulus (G′) values with increased CB concentration. Furthermore, these hydrogels exhibited excellent self-healing, shear-thinning, and tissue-adhesive properties. Notably, the hydrogels successfully sealed the incision site with suturing, resulting in a significant increase in the bursting pressure. The proposed self-healing and adhesive hydrogels are potentially useful in versatile biomedical applications, particularly as suture support materials for surgical procedures.
... The functionalization with catechol groups can also prevent contaminations related to surgical procedures [98,106], quench reactive radical species (ROS) [106,107] and inhibit lipid peroxidation [108]. Furthermore, catechol-functionalized hydrogels also have antiinflammatory activity that is exerted through the inhibition of three enzymes: elastase, collagenase and peroxidase, which are overexpressed in chronic wounds [109]. ...
... The functionalization with catechol groups can also prevent contaminations related to surgical procedures [98,106], quench reactive radical species (ROS) [106,107] and inhibit lipid peroxidation [108]. Furthermore, catechol-functionalized hydrogels also have antiinflammatory activity that is exerted through the inhibition of three enzymes: elastase, collagenase and peroxidase, which are overexpressed in chronic wounds [109]. ...
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The central nervous system (CNS) has a limited ability to regenerate after a traumatic injury or a disease due to the low capacity of the neurons to re-grow and the inhibitory environment formed in situ. Current therapies include the use of drugs and rehabilitation, which do not fully restore the CNS functions and only delay the pathology progression. Tissue engineering offers a simple and versatile solution for this problem through the use of bioconstructs that promote nerve tissue repair by bridging cavity spaces. In this approach, the choice of biomaterial is crucial. Herein, we present recent advances in the design and development of adhesive and self-healing materials that support CNS healing. The adhesive materials have the advantage of promoting recovery without the use of needles or sewing, while the self-healing materials have the capacity to restore the tissue integrity without the need for external intervention. These materials can be used alone or in combination with cells and/or bioactive agents to control the inflammation, formation of free radicals, and proteases activity. We discuss the advantages and drawbacks of different systems. The remaining challenges that can bring these materials to clinical reality are also briefly presented.
... This process is closely associated with inflammatory cells, especially macrophages and granulocytes [56]. Catechol is a natural antioxidant that quenches the excess reactive oxygen species (ROS)/reactive nitrogen species (RNS) produced at the site of inflammation, preventing tissue damage and inducing the production of antiinflammatory mediators [33,57,58]. It had to be checked whether the antioxidant and antiinflammatory characteristics of catechol were successfully engrafted in the C-PU-PTMEG polymers. ...
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Many polyurethanes (PUs) are blood-contacting materials due to their good mechanical properties, fatigue resistance, cytocompatibility, biosafety, and relatively good hemocompatibility. Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications. Herein, a series of catechol functionalized PU (C-PU-PTMEG) elastomers containing variable molecular weight of polytetramethylene ether glycol (PTMEG) soft segment are reported by stepwise polymerization and further introduction of catechol. Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content, mobility of the chain segment, hydrogen bond and microphase separation of the C-PU-PTMEG elastomers, thus offering tunability of mechanical strength (such as breaking strength from 1.3 MPa to 5.7 MPa), adhesion, self-healing efficiency (from 14.9% to 96.7% within 2 hours), anticoagulant, antioxidation, anti-inflammatory properties and cellular growth behavior. As cardiovascular stent coatings, the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure. Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells, inhibit smooth muscle cell proliferation, mediate inflammatory response, and reduce thrombus formation. With the universality of surface adhesion and tunable multifunctionality, these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.
... 3D printers have attracted great attention in tissue engineering applications, especially manufacturing polymeric scaffolds, because they can overcome some limitations of traditional methods197 . Besides, bioactivity and cellular interactions of the designed scaffolds may be increased via the incorporation of catecholcontaining moieties198 . Based on this idea, PDA-coated 3D printed PLA scaffolds with enhanced bioactivity were fabricated using a relatively simple one-step procedure199 .Furthermore, PDA coating facilitates the immobilization of type I collagen (COL I) onto the surface. ...
... Catecholcontaining HCA side chains provide wet adhesion for the copolymer. The biocompatible membrane shows an anti-inflammatory effect and ultraviolet screening properties as well198 .Conjugated N-vinyl caprolactam (V) and 2-hydroxyethyl methacrylate (H) with catechol to produce a biocompatible tissue adhesive for wound healing198 .The scar is a fibrous connective tissue that may replace the healthy tissues after the wound heals. In scar tissue, small collagen bundles are aligned parallel to each other while normal tissue is composed of collagens with random basketweave structure 245 . ...
... Catecholcontaining HCA side chains provide wet adhesion for the copolymer. The biocompatible membrane shows an anti-inflammatory effect and ultraviolet screening properties as well198 .Conjugated N-vinyl caprolactam (V) and 2-hydroxyethyl methacrylate (H) with catechol to produce a biocompatible tissue adhesive for wound healing198 .The scar is a fibrous connective tissue that may replace the healthy tissues after the wound heals. In scar tissue, small collagen bundles are aligned parallel to each other while normal tissue is composed of collagens with random basketweave structure 245 . ...
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After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis—blue mussel and Mytilus californianus—California mussel are the most well‐known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle‐inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle‐inspired biomaterials in various medical applications are summarized for future developments in the field.
... For instance, mussels show extremely good adhesion with high binding strength to various surfaces under wet conditions [131][132][133]. It was found that the catechol unit is the main factor that allows mussels to adhere to a variety of surfaces [134,135]. Materials containing catechol units can be used to create covalent and non-covalent attachments to various substrates for many medical applications, including drug delivery systems and wound healing [47,136,137]. Therefore, inspiration from nature provides enormous information on how to develop materials with versatile adhesion capacities for both wet and dry surfaces. ...
... Therefore, scaffold porosity is a must for homogenous cell distribution and interconnection throughout engineered tissues [156,157]. Additionally, pore size can have an effect on the cell growth, vascularization, nutrients and oxygen diffusion, especially in the absence of a functional vascular system [133][134][135][158][159][160]. Various techniques, components and ratios are used to obtain controlled pore size and architecture scaffolds. ...
Article
Full-text available
Novel advanced biomaterials have recently gained great attention, especially in minimally invasive surgical techniques. By applying sophisticated design and engineering methods, various elastomer–hydrogel systems (EHS) with outstanding performance have been developed in the last decades. These systems composed of elastomers and hydrogels are very attractive due to their high biocompatibility, injectability, controlled porosity and often antimicrobial properties. Moreover, their elastomeric properties and bioadhesiveness are making them suitable for soft tissue engineering. Herein, we present the advances in the current state-of-the-art design principles and strategies for strong interface formation inspired by nature (bio-inspiration), the diverse properties and applications of elastomer–hydrogel systems in different medical fields, in particular, in tissue engineering. The functionalities of these systems, including adhesive properties, injectability, antimicrobial properties and degradability, applicable to tissue engineering will be discussed in a context of future efforts towards the development of advanced biomaterials.
... For instance, mussels show extremely good adhesion with high binding strength to various surfaces under wet conditions [131][132][133]. It was found that the catechol unit is the main factor that allows mussels to adhere to a variety of surfaces [134,135]. Materials containing catechol units can be used to create covalent and non-covalent attachments to various substrates for many medical applications, including drug delivery systems and wound healing [47,136,137]. Therefore, inspiration from nature provides enormous information on how to develop materials with versatile adhesion capacities for both wet and dry surfaces. ...
... Therefore, scaffold porosity is a must for homogenous cell distribution and interconnection throughout engineered tissues [156,157]. Additionally, pore size can have an effect on the cell growth, vascularization, nutrients and oxygen diffusion, especially in the absence of a functional vascular system [133][134][135][158][159][160]. Various techniques, components and ratios are used to obtain controlled pore size and architecture scaffolds. ...
Preprint
Full-text available
Novel advanced biomaterials have recently gained great attention, especially in surgical minimally invasive techniques. Applying sophisticated design and engineering methods, various elastomer-hydrogel systems (EHS) with outstanding performance have been developed in last decades. Those systems composed of elastomers and hydrogels are very attractive due to their high biocompatibility, injectability, controlled porosity and often antimicrobial properties. Moreover, elastomeric properties and bioadhesiveness are making them suitable for soft tissue engineering. Herein, we present the advances in current state-of-the-art design principles and strategies for strong interface formation inspired by nature (bio-inspiration), diverse properties and applications of elastomer-hydrogel systems in different medical fields, in particular, in tissue engineering. Functionalities of those systems, including adhesive properties, injectability, antimicrobial properties and degradability applicable to tissue engineering will be discussed in a context of future efforts towards development of advanced biomaterials.
... Added value can be their injectability or controlled porosity making them suitable for tissue engineering applications [3]. Moreover, elastomeric properties and bioadhesiveness can make them suitable for soft tissue repair [4]. In this study, we present the synthesis of amphiphilic hybrid networks consisting fatty acid derived ester-urethane telechelic macromonomer and PEGylated fibrinogen to create amphiphilic polymer networks. ...
... Compared to conventional wound dressings, such as gauze and films, bioadhesive hydrogels are biologically more compatible and can be removed more easily from the wound. The bioadhesive property can be provided to the hydrogel dressings by modification with polyphenol derived moieties, such as catechol, dopamine, gallic acid, or tannic acid [51,52,58,79,80]. ...
Article
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Chronic wounds severely affect 1–2% of the population in developed countries. It has been reported that nearly 6.5 million people in the United States suffer from at least one chronic wound in their lifetime. The treatment of chronic wounds is critical for maintaining the physical and mental well-being of patients and improving their quality of life. There are a host of methods for the treatment of chronic wounds, including debridement, hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy, skin grafts, and hydrogel dressings. Among these, hydrogel dressings represent a promising and viable choice because their tunable functional properties, such as biodegradability, adhesivity, and antimicrobial, anti-inflammatory, and pre-angiogenic bioactivities, can accelerate the healing of chronic wounds. This review summarizes the types of chronic wounds, phases of the healing process, and key therapeutic approaches. Hydrogel-based dressings are reviewed for their multifunctional properties and their advantages for the treatment of chronic wounds. Examples of commercially available hydrogel dressings are also provided to demonstrate their effectiveness over other types of wound dressings for chronic wound healing.
... In addition to the high adhesive properties, catechol groups can quench free radicals (ROS) and inhibit the inflammatory response, promoting wound healing. Moreover, the strong adhesion between the material and the tissue can act as a preventive barrier against microbial infection without compromising the moist needed for wound healing [20][21][22][23][24]. 3, 4-dihydroxybenzaldehyde (3,4-DB), a catechol derivative, has anti-proliferative, anti-atherosclerotic, anti-fibrogenic, anti-inflammatory and anti-bacterial properties [25,26]. ...
Article
We describe bioadhesive membranes developed from marine renewable biomaterials, namely chitosan and collagen extracted from fish skins. Collagen was functionalized with catechol groups (Coll-Cat) to provide the membranes with superior adhesive properties in a wet environment and blended with chitosan to improve the mechanical properties. The blended membranes were compared to chitosan and chitosan blended with unmodified collagen in terms of surface morphology, wettability, weight loss, water uptake, mechanical and adhesive properties. The metabolic activity, the viability and the morphology of L929 fibroblastic cells seeded on these membranes were also assessed. Our results show that the functionalization with catechol groups improves the adhesive and mechanical properties of the membranes and enhances cell attachment and proliferation. These data suggest that the developed marine origin-raw membranes present a potential towards the restoration of the structural and functional properties of damaged soft tissues.
... Also, RA ability to reduce LPS-induced nitric oxide levels was assessed and used for comparative purposes. Different authors already proved the capacity of rosmarinic acid and catechol bearing formulations to attenuate nitric oxide production after activation with LPS (Silveira Fachel et al., 2019;Puertas-Bartolomé et al., 2018;Qiao et al., 2005). Fig. 6 shows the total amount of NO released by LPS-stimulated cells expressed in percentage after treatment with RA samples at different concentrations (Fig. 6A) or lixiviate samples (Fig. 6B). ...
Article
Full-text available
Rosmarinic acid is an attractive candidate for skin applications because of its antioxidant, anti-inflammatory, and photoprotective functions, however, its poor bioavailability hampers its therapeutic outcome. In this context, synthesis of polymer conjugates is an alternative to enlarge its applications. This work describes the synthesis of novel water-soluble chitosan – rosmarinic acid conjugates (CSRA) that have great potential for skin applications. Chitosan was functionalized with different contents of rosmarinic acid as confirmed by ATR-FTIR, ¹H NMR and UV spectroscopies. CSRA conjugates presented three-fold radical scavenger capacity compared to the free phenolic compound. Films were prepared by solvent-casting procedure and the biological activity of the lixiviates was studied in vitro. Results revealed that lixiviates reduced activation of inflamed macrophages, improved antibacterial capacity against E. coli with respect to native chitosan and free rosmarinic acid, and also attenuated UVB-induced cellular damage and reactive oxygen species production in fibroblasts and keratinocytes.