New formaldehyde-free adhesives for wood manufacturing: In vitro evaluation of potential toxicity of fine dust collected during wood sawing using a new experimental model to simulate occupational inhalation exposure.

Formaldehyde mainly emitted from wood adhesives, finishing materials, paint for furniture represents, together with wood dust, a potential carcinogenic risk for wood workers. Aims of this multidisciplinary study are to investigate the possibility of replacing urea-formaldehyde (UF) adhesives in the wood industry with organic and/or inorganic-based glues to obtain a final less toxic product and to evaluate the potential toxicity of wood glued with such new adhesives. For this purpose we selected poplar wood to test an organic new adhesive HBP (Hemp Based Protein), a mixture of hemp flour and cross-linker PAE (polyaminoamide epichlorohydrin), and spruce wood to test an inorganic adhesive geopolymer K-PSS (potassium-polysiloxosialate) plus polyvinyl acetate. For the poplar wood, we also used a commercial panel glued with UF for comparison. We reproduced occupational inhalation exposure during sawing activities of mentioned woods, collected and characterized the wood dusts emitted during sawing and evaluated in vitro their potential cyto-genotoxic and inflammatory effects. We used human lung cells (A549) exposed for 24 h to 20 and 100 µg/mL of collected PM2.5 wood dust. We found that both the new adhesives wood dusts induced a slightly higher apoptotic effect than untreated natural wood dusts particularly in spruce wood. Only geopolymer K-PSS wood dust induced membrane damage at the highest concentration and direct and oxidative DNA damage that could be explained by the different chemical composition and the lower particle sizes in respect to organic HBP adhesive wood dust. We found slight induction of IL-6 release, not influenced by K-PSS treatment, at the highest concentration in spruce wood. For poplar wood, IL-6 and IL-8 induction was found particularly for untreated and UF-treated wood at the highest concentration, where hemp adhesive treatment induced lower inflammation while at lower concentration similar slight cytokine induction was found for all tested wood dusts. This preliminary study shows that natural adhesives used to replace UF adhesives represent an interesting alternative, particularly the organic hemp-based adhesive showing very low toxicity.

A catechol-chitosan-based adhesive and injectable hydrogel resistant to oxidation and compatible with cell therapy.

Injectable hydrogels designed for cell therapy need to be adhesive to the surrounding tissues to maximize their retention and the communication between the host and the encapsulated cells. Catechol grafting is an efficient and well-known strategy to improve the adhesive properties of various polymers, including chitosan. However, catechol groups are also known to be cytotoxic as they oxidize into quinones in alkaline environments. Usually, hydrogels made from catechol-grafted chitosan (cat-CH) oxidize quickly, which tends to limit adhesion and prevent cell encapsulation. In this work, we limited oxidation and improved the cytocompatibility of cat-CH hydrogels by grafting chitosan with dihydroxybenzoic acid (DHBA), a small cat-bearing molecule known to have a high resistance to oxidation. We show that DHBA-grafted CH (dhba-CH) oxidized significantly slower and to a lesser extent that cat-CH made with hydrocaffeic acid (hca-CH). By combining dhba-CH with sodium bicarbonate and phosphate buffer, we fabricated thermosensitive injectable hydrogels with higher mechanical properties, quicker gelation and significantly lower oxidation than previously designed cat-CH systems. The resulting gels are highly adhesive on inorganic substrates and support L929 fibroblast encapsulation with high viability (≥90% after 24 hours), something that was not possible in any previously designed cat-CH gel system. These properties make the dhba-CH hydrogels excellent candidates for minimally invasive and targeted cell therapy in applications that require high adhesive strength.

Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization.

Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with ∼140% stretchability and ∼19 000 J/m3 toughness, which correspond to ∼5.7 and ∼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (∼4.0 and ∼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.

Mussel-Inspired Bisphosphonated Injectable Nanocomposite Hydrogels with Adhesive, Self-Healing, and Osteogenic Properties for Bone Regeneration.

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.

A high-strength double network polydopamine nanocomposite hydrogel for adhesion under seawater.

Mussel-inspired catechol-based strategy has been widely used in the development of underwater adhesives. Nonetheless, the properties of the adhesives were still severely limited under harsh environments. A facile approach was proposed herein to prepare a double network hydrogel adhesive with low swelling rate and high strength in seawater, where the first network was polyacrylamide (PAM) and the second network was alginate (Alg). Meanwhile, polydopamine (PDA) nanoparticles, which were formed through self-polymerization as adhesion anchoring sites, distributed evenly throughout the double network hydrogel and effectively enhanced the adhesion capability of the hydrogel. The properties of the resulting hydrogel have been fully characterized. The optimal adhesion strength of the hydrogel adhesive in seawater was as high as 146.84 ± 7.78 kPa. Furthermore, the hydrogel also has excellent ability to promote the growth of zooxanthellae. Our studies provide useful insights into the rational design of underwater adhesives with high performances even beyond nature.

Antibacterial, Self-Adhesive, Recyclable, and Tough Conductive Composite Hydrogels for Ultrasensitive Strain Sensing.

Owing to the characteristics of mimicking human skin's function and transmitting sensory signals, electronic skin (e-skin), as an emerging and exciting research field, has inspired tremendous efforts in the biomedical field. However, it is frustrating that most e-skins are prone to bacterial infections, resulting a serious threat to human health. Therefore, the construction of e-skin with an integrated perceptual signal and antibacterial properties is highly desirable. Herein, the dynamic supramolecular hydrogel was prepared through a freezing/thawing method by cross-linking the conductive graphene (G), biocompatible polyvinyl alcohol (PVA), self-adhesive polydopamine (PDA), and in situ formation antibacterial silver nanoparticles (AgNPs). Having fabricated the hierarchical network structure, the PVA-G-PDA-AgNPs composite hydrogel with a tensile strength of 1.174 MPa and an elongation of 331% paves way for flexible e-skins. Notably, the PVA-G-PDA-AgNPs hydrogel exhibits outstanding antibacterial activity to typical pathogenic microbes (e.g., Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus), which effectively prevents bacterial infections that harm human health. With self-adhesiveness to various surfaces and excellent conductivity, the PVA-G-PDA-AgNPs composite hydrogel was used as strain sensors to detect a variety of macroscale and microscale human motions successfully. Meanwhile, the excellent rehealing property allows the hydrogel to recycle as a new sensor to detect large-scale human activities or tiny movement. Based on these remarkable features, the antibacterial, self-adhesive, recyclable, and tough conductive composite hydrogels possess the great promising application in biomedical materials.

VATA: A Poly(vinyl alcohol)- and Tannic Acid-Based Nontoxic Underwater Adhesive.

Few studies aiming to develop a glue with an underwater reusable adhesive property have been reported because combining the two properties of reusable adhesion and underwater adhesion into a single glue formulation is a challenging issue. Herein, preparation of a simple mixture of poly(vinyl alcohol) (PVA) and a well-known phenolic compound, namely, tannic acid (TA), results in an underwater glue exhibiting reusable adhesion. We named the adhesive VATA (PVA + TA). Using VATA, two stainless steel objects (0.77 kg each) are able to be instantly attached. In addition to the high adhesive strength, surface-applied VATA in water retains its adhesive capability even after 24 h. In contrast, cyanoacrylate applied under the same water condition rapidly loses its adhesive power. Another advantage is that VATA's adhesion is reusable. Bonded objects can be forcibly detached, and then the detached ones can be reattached by the residual VATA. VATA maintains nearly 100% of its initial adhesive force, even after 10 repetitions of attach-detach cycles. VATA bonds various materials ranging from metals and polymers to ceramics. Particularly, we first attempt to test the toxicity of the underwater adhesives using an invertebrate nematode, Caenorhabditis elegans and gold fish (vertebrate) due to potential release to the environment.

In Vitro Cytotoxicity of Self-Adhesive Dual-Cured Resin Cement Polymerized Beneath Three Different Cusp Inclinations of Zirconia.

The aim of the present study was to evaluate the in vitro cytotoxicity of self-adhesive dual-cured resin cement (SADRC) polymerized beneath three different cusp inclinations of zirconia with different light curing time. A commercial SADRC (Multilink Speed) was polymerized beneath zirconia (ZrO2) with three different cusp inclinations (0°, 20°, and 30°) for 20 s or 40 s. After being stored in light-proof box for 24 h, the ZrO2-SADRC specimens were immersed in DMEM for 72 h and then we got the extract solution, cultured the human gingival fibroblasts (HGF, 8 × 103 per well) with 100% or 50% concentrations of the extract solution for 24 h, 72 h, and 120 h, respectively, and evaluated cytotoxicity of the polymerized SADRC with CCK-8 assay in optical density (OD) values, relative growth rates (RGR), and cytotoxicity grades. Statistical analysis was conducted using a two-way ANOVA followed by post hoc Student-Newman-Keuls test. The OD values varied from 0.8930 to 3.2920, the RGR varied from 33.93% to 98.68%, and the cytotoxicity grades varied from 0 to 2. There was significant difference in the OD values among the different cusp inclinations of zirconia (P < 0.001), and there was significant difference in the OD values between the different light curing times in some situations (P < 0.05). The cusp inclination of zirconia affects the in vitro cytotoxicity of SADRC. Prolonging the light curing time from 20 s to 40 s can reduce the in vitro cytotoxicity of SADRC when the cusp inclination of zirconia is smaller than 20°.

Toxicity-Attenuated Glycol Chitosan Adhesive Inspired by Mussel Adhesion Mechanisms.

Chitosan-catechol, inspired from mussel-adhesive-proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan-catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan-catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol-conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan-catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan-catechol and glycol chitosan-catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan-catechol significantly attenuates the immune response compared with chitosan-catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan-catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan-catechol. This study suggests that glycol chitosan-catechol can be a promising alternative to chitosan-catechol in various biomedical fields such as hemostatic agents.

Entirely S-Protected Thiolated Silicone: A Novel Hydrophobic Mucoadhesive and Skin Adhesive.

The aim of this study was the synthesis and evaluation of an entirely S-protected thiolated silicone as novel hydrophobic mucoadhesive and skin adhesive. 2-[(2-Amino-2-carboxyethyl)disulfanyl]nicotinic acid was covalently attached to a poly(dimethylsiloxane)-graft-polyacrylate via amide bond formation. Adhesive properties were determined via the rotating cylinder method and tensile studies on porcine small intestinal mucosa besides on porcine abdominal skin. Rheological characteristics were evaluated on a cone-plate rheometer. The S-protected thiolated silicone exhibited 128 ± 18 µmol immobilized 2-mercaptonicotinic acid per gram of polymer and showed a 5.9-fold extended time of mucosal adhesion compared with the unmodified silicone on the rotating cylinder. With a 2.3-fold higher maximum detachment force and a 1.7-fold higher total work of adhesion tested on porcine small intestinal mucosa, the S-protected thiolated silicone is superior to the unmodified silicone. Furthermore, using porcine abdominal skin, a 2.4-fold higher maximum detachment force and a 4.4-fold higher total work of adhesion obtained for the S-protected thiolated silicone outlines the preferentially adhesion to skin. Triggered by N-acetyl-L-cysteine liberated thiol groups form interchain and intrachain disulfide bonds within the polymer (6.7% m/v) causing a 23.0-fold increase in dynamic viscosity (ƞ). In parallel, the elastic modulus (G') and the viscous modulus (G") increased 39.2-fold and 8.1-fold, respectively.

[Evaluation of the Cytotoxicity of Commercially Available Nail Adhesives].

Nail tips are nail art materials that can be attached to the nail with adhesives. Recently, nail/finger injuries related to nail tips have been reported and one of the causes is considered to be the adhesives used for attaching nail tips. The components of nail adhesives are mostly cyanoacrylate, which is also used as an industrial instant adhesive. During curing, cyanoacrylate adhesives release formaldehyde through hydrolysis. When it is marketed as a nail adhesive, there is no regulation regarding its formaldehyde amount nor obligation to indicate its ingredients in Japan. Additionally, a biological safety test is not required for nail adhesives. Thus, because the safety of nail adhesives is inadequately confirmed, it is necessary to investigate their biological safety. Therefore, we purchased 5 commercially available nail adhesives and 1 medical adhesive and examined their formaldehyde content and cytotoxicity. We examined the cytotoxicity of the adhesives in V79 cells by a colony forming assay. In this test, 5 nail adhesives showed higher toxicity than 1 medical adhesive. Formaldehyde concentrations in the extract of adhesives were as follows: 17.5 to 24.2 µg/mL for nail adhesives and 7.4 µg/mL for medical adhesives. Cyanoacetate did not elicit cytotoxicity at the final concentration up to 1000 µM. However, formaldehyde showed cytotoxicity, with an IC50 of 79 µM (2.4 µg/mL). Taken together, the cytotoxicity of nail adhesives could be due to the formaldehyde generated by the hydrolysis of cyanoacrylate. It seems important that nail adhesives will be regulated by obligation and enhanced safety in the future.

An integrative investigation of the therapeutic mechanism of Ainsliaea fragrans Champ. in cervicitis using liquid chromatography tandem mass spectrometry based on a rat plasma metabolomics strategy.

Cervicitis is an extremely common gynecological disease and can be induced by diverse factors such as Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium infections. Long-term unhealed cervicitis may lead to a series of diseases including endometritis, salpingitis, pelvic inflammatory disease, and chorioamnionitis. However, the pathogenesis of cervicitis remains unknown. Ainsliaea fragrans Champ. (AFC) has been widely used in clinical treatment of cervicitis. In the present study, we performed an integrative investigation involving histopathology analysis and non-target plasma metabolomics analysis in a cervicitis rat model induced by phenol mucilage, using ultra-performance liquid chromatography coupled with a tandem quadrupole time-of-flight mass spectrometry approach. Based on the integrative investigation, marked metabolomic differences were identified between the cervicitis and control groups using multivariate analysis. As a result, 32 potential biomarkers were identified in the response to cervicitis, and were involved in arachidonic acid metabolism, linoleic acid metabolism, primary bile acid biosynthesis, taurine and hypotaurine metabolism, pantothenate and CoA biosynthesis, and glycerophospholipid metabolism. After treatment, a total of 27 potential biomarkers exhibited altered levels in the AFC group compared to the model group, and 12 metabolites including 1-stearoylglycerophosphoinositol, bolasterone, lysoPC(16:0), lysoPC(20:4), lysoPC(P-16:0), lysoPC(P-18:0), lysoPC(P-18:1), stearoylcarnitine, taurine, lysoPC(17:0), 20-hydroxyeicosatetraenoic acid, and 1-arachidonoylglycerophosphoinositol returned to their normal levels. This study suggested that the therapeutic mechanism of AFC is related to those altered endogenous metabolites.

Evaluation of dermal adhesive formulations for topical application.

Topical delivery is one of the main challenges in the pharmaceutical technology. This study aimed to synthesize a potential adhesive polymeric excipient stable enough for pronounced skin adhesiveness to pave the skin delivery pathway. Polyacrylic acid an anionic well established polymer in the pharmaceutical field was chemically modified with sulfhydryl moieties and in a second step, this sulfhydryl bearing polymer was prone to a preactivation process. During this process, mercaptonicotinic acid was covalently bound to the sulfhydryl groups of polyacrylic acid. The obtained polymeric conjugates were characterized with respect to viscosity measurements, and evaluated in terms of skin adhesive properties with the help of tensile strength assay as well as bond strength assay. Findings exhibited promising potential of newly synthesized preactivated polyacrylic acid in terms of adhesive properties. Preactivated polyacrylic acid revealed a 15.39-fold improved adhesion compared to unmodified polymeric excipient. Therefore, the herein designed preactivated polyacrylic acid shows interesting features for skin application such as scar and wound management.

[Dangerous cosmetic products in Germany : Analysis of the RAPEX database of the European Commission]. / Gefährliche Kosmetikprodukte in Deutschland : Analyse der RAPEX-Datenbank der Europäischen Kommission.

BACKGROUND: Cosmetic products are subject to the European Cosmetics Regulation: They shall not harm human health when used under "normal or reasonably foreseeable conditions". Hazardous cosmetic products are reported by the EU Member States to the EU Commission and are listed in the database of the European Rapid Alert System RAPEX. MATERIAL AND METHODS: The reports from Germany on dangerous cosmetic products from the years 2005-3/2017 in the European RAPEX database were systematically analyzed. RESULTS: During the study period, 157 dangerous cosmetic products were reported from Germany. The most common product categories were bleaching creams (24.2%) because of the content of hydroquinone, mercury or corticosteroids, creams/lotions/gels (10.8%) mainly due to microbiological contamination, henna products (10.2%) because of sensitizing concentrations of paraphenylene diamine, and nail adhesives (8.9%) because of high levels of methyl methacrylate. CONCLUSIONS: Hazardous cosmetic products appear to be rare in view of the high market volume of cosmetics, even though the total number of official investigations the RAPEX reports based on is not known. Dermatologists should inform the competent monitoring authorities in case of a suspected harm to health caused by dangerous cosmetic products so that the products can be examined and, if necessary, withdrawn from the market.

Occupational asthma caused by acrylic compounds from SHIELD surveillance (1989-2014).

BACKGROUND: Acrylic monomers (acrylates), methacrylates and cyanoacrylates all cause asthma by respiratory sensitization. Occupational inhalation exposures occur across a variety of industries including health care and dental work, beauty, laboratory science, assembly and plastic moulding. AIMS: To examine notifications of occupational asthma caused by acrylic compounds from a UK-based regional surveillance scheme, in order to highlight prevalent exposures and trends in presentation. METHODS: Retrospective review of all cases reported to the SHIELD surveillance scheme for occupational asthma, West Midlands, UK between 1989 and 2014. Patient data were gathered on demographics, employment, asthma symptoms and diagnostic investigations including serum immunological testing, serial peak flow analysis and specific inhalation challenge tests. Descriptive statistics were used to illustrate worker characteristics and evidence for sensitization to acrylic compounds. RESULTS: There were 20 affected patients out of 1790 total cases of occupational asthma (1%); all cases were confirmed by OASYS (Occupational Asthma SYStem) analysis of serial peak flow measurements, with three additional positive specific inhalation challenge tests. Three out of 20 (15%) patients were current smokers and 11/20 (55%) were atopic. A variety of exposures and industries were implicated including: manufacturing, health care, beauty and printing and a novel presentation seen in teachers exposed to floor adhesives. CONCLUSIONS: This is the largest reported series of occupational asthma caused by acrylic compounds, which remain an important aetiological factor in this disease. Exposure occurs in a variety of industries, particularly in manufacturing and is seen with other, perhaps better recognized sensitizing agents such as isocyanates and epoxy resins.

Migration assessment and the 'threshold of toxicological concern' applied to the safe design of an acrylic adhesive for food-contact laminates.

The suitability of an acrylic adhesive used on food packaging was studied. Six potential migrants were identified using GC-MS and UPLC-QTOF. Five compounds were intentionally added (2-butoxyethanol and 2,4,7,9-tetramethyl-5-decyne-4,7-diol 10 (TMDD) and TMDD ethoxylates). One of the compounds identified as 2-(12-(methacryloyloxy) dodecyl)malonic acid was a non -intentionally added substance (NIAS), which could be a methyl metacrylate derivative. A migration study from multilayers containing paper-adhesive-film was carried out. The films used were polyethylene (PE), polypropylene, polyethylene terephthalate, polylactic acid (PLA) and Ecovio F2223®, which is a mixture of biodegradable polyester with PLA. All the non-volatile compounds, including the identified NIAS, migrated into the dry food simulant Tenax ®. Five surfactants based on TMDD were found to migrate from all laminates into Tenax at levels from 0.05 to 0.6 mg kg-1. The results showed that the lowest migration (0.01 mg kg-1 for 2-(12-(methacryloyloxy)dodecyl)malonic acid to 0.07 for TMDD mg kg-1) occurred when the compounds passed through PLA, demonstrating its functional barrier properties to these compounds. In contrast, PE showed the worst barrier properties to these compounds. To evaluate the migration results, the threshold of toxicological concern strategy was applied. The migration values of the surfactant identified were above 0.09 mg kg-1. Thus, it was decided to remove this surfactant from the formulation.

Strong tissue glue with tunable elasticity.

Many bio-adhesive materials adhere weakly to tissue due to their high water content and weak structural integrity. Others provide desirable adhesive strength but suffer from rigid structure and lack of elasticity after administration. We have developed two water-free, liquid four-armed PEG pre-polymers modified with NHS or with NH2 end groups which upon mixing changed from liquids to an elastic solid. The sealant and adhesive properties increased with the amount of the %v/v PEG4-NHS pre-polymer, and achieved adhesive properties comparable to those of cyanoacrylate glues. All mixtures showed minimal cytotoxicity in vitro. Mixtures of 90%v/v PEG4-NHS were retained in the subcutaneous space in vivo for up to 14days with minimal inflammation. This material's combination of desirable mechanical properties and biocompatibility has potential in numerous biomedical applications. STATEMENT OF SIGNIFICANCE: Many bio-adhesive materials adhere weakly to tissue (e.g. hydrogels) due to their high water content and weak structural integrity. Others provide desirable mechanical properties but suffer from poor biocompatibility (e.g. cyanoacrylates). This study proposes a new concept for the formation of super strong and tunable tissue glues. Our bio-materials' enhanced performance is the product of new neat (without water or other solvents) liquid polymers that solidify after administration while allowing interactions with the tissue. Moreover, the elastic modulus of these materials could easily be tuned without compromising biocompatibility. This system could be an attractive alternative to sutures and staples since it can be applied more quickly, causes less pain and may require less equipment while maintaining the desired adhesion strength.

Cytocompatibility studies of a biomimetic copolymer with simplified structure and high-strength adhesion.

The development of adhesives suitable for biomedical applications has been challenging given that these materials must exhibit sufficient adhesion strengths and biocompatibility. Biomimetic materials inspired by mussel adhesive proteins appear to contain many of the necessary characteristics for biomedical adhesives. In particular, poly[(3,4-dihydroxystyrene)-co-styrene] has been shown to be a high strength adhesive material with bonding comparable to or even greater than several commercial glues. Herein, a thorough study on the cytocompatibility of this copolymer provides insights on the suitability of a mussel-mimicking adhesive for applications development. The cytotoxicity of poly[(3,4-dihydroxystyrene)-co-styrene] was evaluated through assessment of the viability, proliferation rate, and morphology of NIH/3T3 fibroblasts when cultured with copolymer extracts or directly in contact with the adhesive. After 1 and 3 days of culture, both the copolymer alone and copolymer cross-linked with periodate exhibited minimal effects on cell viability. Likewise, cells cultured on the copolymer displayed proliferation rates and morphologies similar to cells on the poly-L-lysine control. These results indicate that poly[(3,4-dihydroxystyrene)-co-styrene] is highly cytocompatible and therefore a promising material for use where biological contact is important.

Photocurable bioadhesive based on lactic acid.

Novel photocurable and low molecular weight oligomers based on l-lactic acid with proven interest to be used as bioadhesive were successfully manufactured. Preparation of lactic acid oligomers with methacrylic end functionalizations was carried out in the absence of catalyst or solvents by self-esterification in two reaction steps: telechelic lactic acid oligomerization with OH end groups and further functionalization with methacrylic anhydride. The final adhesive composition was achieved by the addition of a reported biocompatible photoinitiator (Irgacure® 2959). Preliminary in vitro biodegradability was investigated by hydrolytic degradation in PBS (pH=7.4) at 37 °C. The adhesion performance was evaluated using glued aminated substrates (gelatine pieces) subjected to pull-to-break test. Surface energy measured by contact angles is lower than the reported values of the skin and blood. The absence of cytoxicity was evaluated using human fibroblasts. A notable antimicrobial behaviour was observed using two bacterial models (Staphylococcus aureus and Escherichia coli). The cured material exhibited a strong thrombogenic character when placed in contact with blood, which can be predicted as a haemostatic effect for bleeding control. This novel material was subjected to an extensive characterization showing great potential for bioadhesive or other biomedical applications where biodegradable and biocompatible photocurable materials are required.