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Abstract: Small cartilage defects are frequently treated with debridement or left untreated, predisposing to early onset osteoarthritis. We propose to fill these defects with a cell-free injectable hydrogel comprising dextran-tyramine conjugates (Dex-TA) that can be applied during arthroscopic procedures. In this study, we report on the adhesion mechanism between cartilage and Dex-TA hydrogels and enhancement of cell ingrowth by incorporation of Heparin-tyramine (Hep-TA) conjugates. The enzyme-catalyzed crosslinking reaction of Dex-TA and Hep-TA hydrogels is based on covalent bonding of hydroxyphenyl residues. We hypothesized that this reaction results in covalent bonding of the hydroxyphenyl residues in Dex-TA and Hep-TA to tyrosine residues in cartilage matrix proteins. The involvement of TA residues was confirmed by modelling the enzymatic reaction occurring during gelation. The mechanical analysis indicated that higher tyramine content led to stronger binding. Interfacial cartilage-hydrogel morphology and Raman spectroscopy demonstrated collagens’ reorganization and evidenced the coupling of TA to tyrosine residues in collagen. Moreover, the addition of Hep-TA induced cell recruitment. Collectively, in vitro and ex vivo functional studies evidenced the covalent bonding of TA-containing hydrogels to tyrosine residues in cartilaginous matrix proteins. Moreover, the cell-attracting ability of these hydrogels could be explored to guide tissue repair in focal cartilage defects, preventing or delaying the onset osteoarthritis. [Copyright &y& Elsevier]

Abstract: The interactions of a number of commercially available dextran preparations with the lectin Concanavalin A (ConA) have been investigated. Dextrans over the molecular mass range 6×103–2×106 gmol−1 were initially characterised in terms of their branching and hence terminal ligand density, using NMR. This showed a range of branching ratios between 3% and 5%, but no clear correlation with molecular mass. The bio-specific interaction of these materials with ConA was investigated using microcalorimetry. The data obtained were interpreted using a number of possible binding models reflecting the known structure of both dextran and the lectin. The results of this analysis suggest that the interaction is most appropriately described in terms of a two-site model. This offers the best compromise for the observed relationship between data and model predictions and the number of parameters used based on the chi-squared values obtained from a nonlinear least-squares fitting procedure. A two-site model is also supported by analysis of the respective sizes of the dextrans and the ConA tetramer. Using this model, the relationship between association constants, binding energy and molecular mass was determined. [Copyright &y& Elsevier]

Abstract: In this study, injectable hydrogels were prepared by horseradish peroxidase-mediated co-crosslinking of dextran–tyramine (Dex–TA) and heparin–tyramine (Hep–TA) conjugates and used as scaffolds for cartilage tissue engineering. The swelling and mechanical properties of these hydrogels can be easily controlled by the Dex–TA/Hep–TA weight ratio. When chondrocytes were incorporated in these gels, cell viability and proliferation were highest for gels with a 50/50 weight ratio of Dex–TA/Hep–TA. Moreover, these hydrogels induced an enhanced production of chondroitin sulfate and a more abundant presence of collagen as compared to Dex–TA hydrogels. The results indicate that injectable Dex–TA/Hep–TA hydrogels are promising scaffolds for cartilage regeneration. [Copyright &y& Elsevier]

Abstract: Polysaccharide hybrids consisting of hyaluronic acid (HA) grafted with a dextran–tyramine conjugate (Dex–TA) were synthesized and investigated as injectable biomimetic hydrogels for cartilage tissue engineering. The design of these hybrids (denoted as HA-g-Dex–TA) is based on the molecular structure of proteoglycans present in the extracellular matrix of native cartilage. Hydrogels of HA-g-Dex–TA were rapidly formed within 2 min via enzymatic crosslinking of the tyramine residues in the presence of horseradish peroxidase and hydrogen peroxide. The gelation time, equilibrium swelling and storage modulus could be adjusted by varying the degree of substitution of tyramine residues and polymer concentration. Bovine chondrocytes incorporated in the HA-g-Dex–TA hydrogels remained viable, as shown by the Live–dead assay. Moreover, enhanced chondrocyte proliferation and matrix production were observed in the HA-g-Dex–TA hydrogels compared to Dex–TA hydrogels. These results suggest that HA-g-Dex–TA hydrogels have a high potential as injectable scaffolds for cartilage tissue engineering. [Copyright &y& Elsevier]

Background: The aim of this study was to compare the anti-adhesion efficacy of a biodegradable, in situ, macromolecular cross-linking hydrogel made from oxidized dextran/N-carboxyethyl chitosan (Odex/CEC) with a commercially available carboxymethylcellulose/modified hyaluronan barrier film (Seprafilm; Genzyme Corporation, Cambridge, MA) in a rat cecum abrasion model. Methods: The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The 2% Odex/CEC hydrogel treatment was applied by syringe to coat both the cecal and the abdominal wall insults, while other animals were treated with Seprafilm applied to the cecal injury only. Control animals did not receive any treatment. Animals were sacrificed after post operative day 21 and adhesion severity was quantitatively graded using a whole number scale from 0 – 3. Histological analysis was also performed for animals receiving Odex/CEC hydrogel treatment and no treatment (control). Results: Mean adhesion score was 2.09±1.22 for control animals, 1.00±1.00 for 2% Odex/CEC hydrogel animals, and 1.25±1.22 for Seprafilm animals. Hydrogel treated animals showed significantly lower adhesion scores than control animals (P <0.05), while Seprafilm demonstrated a marginally lower adhesion score (P <0.1) compared with the controls. Histological analysis of an Odex/CEC treated rat showed tissue repair and small fragments of hydrogel inside both healed abdominal and cecal surfaces. Conclusions: Both Seprafilm and the 2% Odex/CEC hydrogel showed a significantly decreased adhesion score compared with the control. However, the hydrogel, compared with Seprafilm, offers ease of application and ability to conform to complex tissue geometries that could provide surgeons with another prophylactic treatment to prevent abdominal adhesions. [Copyright &y& Elsevier]

Abstract: Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, vitamin E (α-tocopherol) was loaded into a dextran hydrogel containing ferulic moieties, covalently linked, to improve its topical delivery, and also to increase its relative poor stability, which is due to direct exposure to UV light. Methacrylic groups were first introduced onto the dextran polymer backbones, then the obtained methacrylated dextran was copolymerized with aminoethyl methacrylate, and subsequently esterificated with trans-ferulic acid. The new biopolymer was characterized by Fourier transform infrared spectroscopy. The values of content of phenolic groups were determined. Its ability in inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a source of free radicals, that is tert-butyl hydroperoxide, was studied. Hydrogel was also characterized for swelling behaviour, vitamin E loading efficiency, release, and deposition on the rabbit skin. Additionally, vitamin E deposition was compared through hydrogels, respectively, containing and not containing trans-ferulic acid. The results showed that ferulate hydrogel was a more effective carrier in protecting vitamin E from photodegradation than hydrogel without antioxidant moieties. Then antioxidant hydrogel could be of potential use for cosmetic and pharmaceutical purposes as carrier of vitamin E that is an antioxidant that reduces erythema, photoaging, photocarcinogenesis, edema, and skin hypersensitivity associated with exposure to ultraviolet B (UVB) radiation, because of its protective effects. [Copyright &y& Elsevier]