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A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 μM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 μM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 μM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18.

Bacterial nanocellulose (BNC) produced by aerobic bacteria is a biopolymer with sophisticated technical properties. Although the potential for economically relevant applications is huge, the cost of BNC still limits its application to a few biomedical devices and the edible product Nata de Coco, made available by traditional fermentation methods in Asian countries. Thus, a wider economic relevance of BNC is still dependent on breakthrough developments on the production technology. On the other hand, the development of modified strains able to overproduce BNC with new properties e.g. porosity, density of fibres crosslinking, mechanical properties, etc. will certainly allow to overcome investment and cost production issues and enlarge the scope of BNC applications. This review discusses current knowledge about the molecular basis of BNC biosynthesis, its regulations and, finally, presents a perspective on the genetic modification of BNC producers made possible by the new tools available for genetic engineering., (undefined), info:eu-repo/semantics/publishedVersion

Vascular grafts are used to bypass damaged or diseased blood vessels. Bacterial cellulose (BC) has been studied for use as an off-the-shelf graft. Herein, we present a novel, cost-effective, method for the production of small caliber BC grafts with minimal processing or requirements. The morphology of the graft wall produced a tensile strength above that of native vessels, performing similarly to the current commercial alternatives. As a result of the production method, the luminal surface of the graft presents similar topography to that of native vessels. We have also studied the in vivo behavior of these BC graft in order to further demonstrate their viability. In these preliminary studies, 1 month patency was achieved, with the presence of neo-vessels and endothelial cells on the luminal surface of the graft.

Poly(l-lactide) electrospun mats with random and aligned fiber orientation and films have been produced with degrees of crystallinity ranging from 0 up to nearly 50%. The overall surface roughness is practically constant irrespective of the sampling areas (1 × 1 µm to 20 × 20 µm) for degrees of crystallinity below 30%, increasing for higher degrees of crystallinity for the larger sampling areas. Further, due to fiber confinement, surface roughness variations are smaller in electrospun mats. Samples with 50% of crystallinity show the lowest osteoblast and the highest fibroblast proliferation. Therefore, it is verified that higher roughness promotes lower osteoblast but higher fibroblast proliferation. The overall results indicate the relevant role of the sub-microenvironment variations associated to the microscale roughness in determining the different cell responses.

An amphiphilic hyaluronic acid conjugate is successfully developed based on grafting a thiolated hydrophobic molecule to the polysaccharide backbone. The engineered conjugate is capable of assembling into nanostructures once dispersed in water, with average diameter of 80.2 � 0.4nm (n ¼5), stable up to 6 months. The thiolated HyA conjugate is reticulated by dissulfide bond with a homofunctional crosslinker—1,4-Bis(3-[2-pyridyldithio]propionamido)butane (DPDPB). The drug loading efficiency of the reticulated and non-reticulated nanogel is accessed with two hydrophobic drugs, curcumin and simvastatin. Results suggest that crosslinked nanogel exhibit higher stability upon dilution and drug loading efficiency and proves to be a redox sensitive material. The nanogels hold great potential as stealth carriers of lipophilic drugs.

A wide variety of biomaterials and bioactive molecules have been applied as scaffolds in neuronal tissue engineering. However, creating devices that enhance the regeneration of nervous system injuries is still a challenge, due the difficulty in providing an appropriate environment for cell growth and differentiation and active stimulation of nerve regeneration. In recent years, bacterial cellulose (BC) has emerged as a promising biomaterial for biomedical applications due its properties, such as high crystallinity, an ultrafine fiber network, high tensile strength and biocompatibility. The small signaling peptides found in the proteins of extracellular matrix are described in the literature as promoters of adhesion and proliferation for several cell lineages on different surfaces. In this work, the peptide IKVAV was fused to a carbohydrate-binding module (CBM3) and used to modify BC surfaces, with the goal of promoting neuronal and mesenchymal stem cell (MSC) adhesion. The recombinant proteins IKVAV-CBM3 and (19)IKVAV-CBM3 were successfully expressed in E. coli, purified through affinity chromatography and stably adsorbed to the BC membranes. The effect of these recombinant proteins, as well as RGD-CBM3, on cell adhesion was evaluated by MTS colorimetric assay. The results showed that the (19)IKVAV-CBM3 was able to significantly improve the adhesion of both neuronal and mesenchymal cells and had no effect on the other cell lineages tested. The MSC neurotrophin expression in cells grown on BC membranes modified with the recombinant proteins was also analyzed., Renata A. N. Pertile gratefully acknowledges support by the Programme Al beta an, the European Union Programme of High Level Scholarships for Latin America (Scholarship No. E07D401931BR). The author Susana Moreira is recipient of a SFRH/BPD/64726/2009 fellowship from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal). Fabia K. Andrade is the recipient of a fellowship from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil).

The principal substance in Narthecium ossifragum (L.) Huds, responsible for the nephrotoxic effects on cattle, moose, goats and other ruminants has been isolated and identified by X-ray crystallography as 3-methoxy-2(5H)-furanone. The Fourier-transform infra-red, 1H and 13C nuclear magnetic resonance, and mass spectra are also given. The concentration in four different batches of plant material varied from 113 to 344 microg g(-1) (wet weight). Extracts of N. ossifragum and fractions derived from them, including purified 3-methoxy-2(5H)-furanone, were each dosed intraruminally, to young goats. 3-Methoxy-2(5H)-furanone of 99.9% purity (15 mg kg(-1) live weight) caused increased concentration of creatinine in serum within 2-3 days, typical of kidney damage caused by N. ossifragum, while toxic effect was obtained down to 4 mg kg(-1) live weight with less purified material (> or = 95%). Toxic effect was also obtained with synthesized 3-methoxy-2(5H)-furanone (30 mg kg(-1) live weight). The isomer 4-methoxy-2(5H)-furanone, detected in some of the batches of the plant material, was not toxic when dosed at 60 mg kg(-1) live weight.

1,3,2-Benzimidazaborole, 1,3,2-benzoxaborole, and 1,3,2-benzothiazaborole were synthesized from the corresponding 2-benzazole N(SINGLE BOND)BH3 and 2-benzazole S(SINGLE BOND)BH3 adducts through a reductive transposition from the isolobal fragment X(SINGLE BOND)C(sp2) (DOUBLE BOND) N(sp2) (SINGLE BOND) B(sp3) (X (DOUBLE BOND) N, O, S) to the fragment X(SINGLE BOND)B(sp2) (DOUBLE BOND) N(sp2) (SINGLE BOND) C(sp3). N(SINGLE BOND)BH3 substitution shifts to lower frequencies 4-H, C-3a, and C-7a resonances. The X-ray diffraction analysis of 2-(o-methoxyphenyl)benzothiazole N(SINGLE BOND)BH3 adduct is reported. Two new tetracyclic boron-bridged compounds were observed as by-products (6,9-(ethyl)-diaza-2-oxa-1-bora[3,4,7,8]-dibenzobycyclo[4.3.0]-nona-3,7-diene, 6d, and 8-aza-9-oxa-2-thia-1-bora-[3,4,7,8]dibenzobycyclo[3.4.0]nona-3,7-diene, 15d, when 2-(o-methoxyphenyl)-1-ethylbenzimidazole-BH36b and 2-(o-methoxyphenyl)-benzothiazole-BH315b adducts were heated. © 1996 John Wiley & Sons, Inc.