Development of a hybrid dextrin hydrogel encapsulating dextrin nanogel as protein delivery system

Dextrin, a glucose polymer with low molecular weight, was used to develop a fully resorbable hydrogel, without using chemical initiators. Dextrin was first oxidized (oDex) with sodium periodate and then cross-linked with adipic acid dihidrazide, a nontoxic cross-linking molecule. Furthermore, a new bidimensional composite hydrogel, made of oxidized dextrin incorporating dextrin nanogels (oDex-nanogel), was also developed. The oDex hydrogels showed good mechanical properties and biocompatibility, allowing the proliferation of mouse embryo fibroblasts 3T3 cultured on top of the gel. The gelation time may be controlled selecting the concentrations of the polymer and reticulating agent. Both the oDex and oDex-nanogel hydrogels are biodegradable and present a 3-D network with a continuous porous structure. The obtained hybrid hydrogel enables the release of the dextrin nanogel over an extended period of time, paralleling the mass loss curve due to the degradation of the material. The dextrin nanogel allowed the efficient incorporation of interleukin-10 and insulin in the oDex hydrogel, providing a sophisticated system of controlled release. The new hydrogels present promising properties as an injectable carrier of bioactive molecules. Both proteins and poorly water-soluble low-molecular-weight drugs are efficiently encapsulated in the nanogel, which performs as a controlled release system entrapped in the hydrogel matrix.V.C. and D.S. were supported by the grants SFRH/BD/27359/2006 and SFRH/BD/64571/2009, respectively, from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. We thank FCT funding through PTDC and COMPETE

A comparative study of reactivity and selectivity of chiral diamines and structurally analogous amino alcohol ligands in enantioselective alkylations with diethylzinc

A series of chiral delta-diamines and structurally analogous delta-amino alcohols derived from natural tartaric acid were synthesized and a comparative study of their activity and selectivity in the enantioselective alkylation of aromatic aldehydes was carried out. Our results show that in general the delta-diamines were found to be better chiral inducers than the corresponding delta-amino alcohols. The highest selectivity was observed when benzaldehyde was alkylated in the presence of the benzylic diamine, giving (R)-1-phenylpropanol with an ee of 42%. Copyright © 2008 John Wiley & Sons, Ltd

Self assembling nanogels

Este resumo faz parte de: Book of abstracts of the Meeting of the Institute for Biotechnology and Bioengineering, 2, Braga, Portugal, 2010. A versão completa do livro de atas está disponível em: http://hdl.handle.net/1822/1096

Development and characterization of an injectable dextrin-based hydrogel for bone regeneration

Bone is a dynamic, highly vascularized tissue that remodels itself continuously over an individual ́s lifetime. It plays several important roles in maintaining homeostasis of the body systems [ 1 , 2 ] . However, this regenerative capac ity is limited and, as in the case of large bone defects, where the template for an orchestrated regeneration is absent, surgical proce dures are needed [ 2 ] . In this respect , bone tissue engineering is a very challe nging and promising field given the need to mimic bone mechanical and biological functions and also due to the failure of current orthoped ic implants. The general concept consists in the development of three - dimensional scaffolds, from biocompatible materials (natu ral or synthetic), which confer temporary support for the regeneration of bone tissue, while the scaffold itself will be resorbed and replaced by new ly formed tissue [ 2 , 3 ] . Hydrogels are cross - linked networks made of natural or synthetic polymers, which are able to support high water contents [ 4 ] . These materials are usua lly biocompatible, have the ability to mimic physiological conditions, promote an environment that can protect cells or unstable drugs, their physical characteristics can be controlled to some extent and some can be injected in vivo . These features make th em attractive materials in the biomedical field for cell encapsulation, drug or gene delivery or to act as an interfa ce between tissue and materials [ 4 - 7 ] . Natural polymers are advantageous for this kind of applications since they are cheap raw materials, bear a great biocompatibility and are usually biodegradable [ 8 ] . Dextrin is low molecular weight carbohydrate, generally regarded as safe (GRAS), obtained from partial hydrolysis of starch or glycogen [ 9 ] . It is a glucose polymer linked by α - 1,4 glycosidic linkages with some degree of branching due to the presence of α - 1,6 bonds [ 10 ] . I t is biocompatible and non - immunogenic, degradable by α - amylases and can undergo renal clearance avoiding tissue accumulation [ 11 , 12 ] . This work describes the preparation and characterization of an injectable dextrin - bas ed hydrogel (oDex) able to incorporate nanoparticles , cells, biomolecules or Bonelike ® granules [ 13 ] . Bonelike ® is a Biosckin - molecular and cell therapies S.A. proprietary synthetic bone graft, and the outcome of the project will result in a novel injectable presentation of this product. The hydrogel was produced by dextrin oxidation with sodium periodate followed by cross - linking with a dihydrazide [ 14 ] . In vitro characterization of oDex hydrogel has shown acceptable m echanical properties, overall good biocompatibility and the ability to be combined with other materials such as a nanogel and urinary bladder matrix, without affecting its structure. The cytotoxicity of the free dihydrazide was evaluated and only a mild in hibitory effect on cell proliferation was observed for the concentration used in the hydrogel crosslinking. The biocompatibilit y of oDex hydrogels was confirmed through the encapsulation of cells, which were able to endure the gelation process. Subcutaneou s implants were performed in Sasco Sprague Dawley rats in order to evaluate the inflammatory response and systemic effects of oDex hydrogels and their combination with Bonelike ® and human mesenchymal stem cells isolated from umbilical cord’s Wharton jelly. After 3 and 15 days post - implantation, a quantitative evaluation of both responses was performed according to ISO 10993 by a scoring system leading to a classification of the implanted material as s light irritant even when associated to Bonelike ® or to the cellular system. The performance of oDex hydrogel combined with Bonelike granules and/or UBM in bone defects was investigated in New Zealand rabbits. Bone defects in several anatomical locations (t ibiae and cranium) of non - critical and critical size were filled with those materials. Histological analysis showed that oDex does not constitute a barrier for cellular colonization and proliferation since the defects that were filled with these materials presented a higher degree of regeneration and a higher amount of collagen fibers with higher organization degrees, when compared with the empty defects. Even though oDex hydrogels purpose is to act as an injectable carrier for osteoconductive materials, li ke Bonelike ® granules, the hydrogel itself seems to assists the regenerative pro cess when compared with the empty defects. This is due to the 3D supp ort conferred by hydrogels that facilitates cell migration to the defect site. Moreover, the presence of UB M strongly stimulates the bone regeneration, for levels comparable with the Bonelike ® conditions, since an increase in cellular colonization and organization in the defect site can be denoted. A sterilization protocol for oDex hydrogels by gamma and beta r adiation was investigated through irradiation of oxidized dextrin solutions. Despite b oth kinds of radiation induced slight differences in the storage modulus of the hydrogels, indicating the occurrence of chain scission/cross - linking effects on the dextri n cha in, all materials were gelable after the irradiation treatments . These effects seem to not be dose or temperature dependent and the irradiation process in liquid or solid state also does not induce major differences in the rheology of the final hydrog els. Due to its known advantages, gamma radiation seems to be a suitable sterilization method for oxidized dextrin solutions. The stability of gamma irradiated dextrin solutions was evaluated up to 8 months. Despite the increase of storage modulus of the h ydrogels over the time, this effect does not constitute a disadvantage since it improves elastic behavior of the hydrogels. oDex hydrogels provides a system that can carry and stabilize cells, nanogels, Bonelike ® granules and other biomolecules. It is a pr omising biomaterial due to its biocompatibility, and potential to promote an adequate environment for bone regeneration. Its injectability allows a minimal invasive surgical procedure with decreased patient morbidity, lower risk of infection and reduced sc ar formation. This work has been developed in the scope of an European project that allowed collaborations with research groups, which have complementary expertise. The tight collaboration between University of Minho and Bioskin S.A. company, envisioning t echnology transfer and product valorization, has resulted in a published international patent of the product ( WO2011070529A2 ) [ 15 ] . Currently, a new set of pre - clinical trials in sheep model s are being planned as well as the submission of a request for the authorization for the clinical trialsGrant SFRH/BD/64571/2009 from Fundação para a Ciência e Tecnologia (FCT), Portugal. We thank FCT funding through EuroNanoMed ENMED/0002/2

Potential of injectable dextrin-based hydrogel for biomedical applications

Bone tissue engineering is a very challenging and promising field, which handles with the limitations of bone regenerative capacity and the failure of current orthopedic implants [1]. This work describes the preparation and characterization of an injectable dextrinbased hydrogel (oDex) through dextrin oxidation followed by cross-linking with a dihydrazide [2]. In vitro and in vivo experiments allowed to conclude that this system can carry and stabilize cells, nanogels, Bonelike® granules [3] and other biomolecules. This is a promising biomaterial due to its biocompatibility, and potential to promote an adequate environment for bone regeneration, which was increased by the combined bioactive molecules. Its injectability allows a minimal invasive surgical procedure with decreased patient morbidity, lower infection risk and reduced scar formation. Furthermore, an adequate sterilization protocol for this kind of material was established. The tight collaboration between University of Minho and Bioskin S.A. company, envisioning technology transfer and product valorization, has resulted in a published international patent of the product (WO2011070529A2) [4]. Currently, the submission of a request for the authorization for the clinical trials is being planned

β-ketoenamine covalent organic frameworks—effects of functionalization on pollutant adsorption

Water pollution due to global economic activity is one of the greatest environmental concerns, and many efforts are currently being made toward developing materials capable of selectively and efficiently removing pollutants and contaminants. A series of β-ketoenamine covalent organic frameworks (COFs) have been synthesized, by reacting 1,3,5-triformylphloroglucinol (TFP) with different C2-functionalized and nonfunctionalized diamines, in order to evaluate the influence of wall functionalization and pore size on the adsorption capacity toward dye and heavy metal pollutants. The obtained COFs were characterized by different techniques. The adsorption of methylene blue (MB), which was used as a model for the adsorption of pharmaceuticals and dyes, was initially evaluated. Adsorption studies showed that –NO2 and –SO3H functional groups were favorable for MB adsorption, with TpBd(SO3H)2-COF [100%], prepared between TFP and 4,4′-diamine- [1,1′-biphenyl]-2,2′-disulfonic acid, achieving the highest adsorption capacity (166 ± 13 mg g−1). The adsorption of anionic pollutants was less effective and decreased, in general, with the increase in –SO3H and –NO2 group content. The effect of ionic interactions on the COF performance was further assessed by carrying out adsorption experiments involving metal ions. Isotherms showed that nonfunctionalized and functionalized COFs were better described by the Langmuir and Freundlich sorption models, respectively, confirming the influence of functionalization on surface heterogeneity. Sorption kinetics experiments were better adjusted according to a second-order rate equation, confirming the existence of surface chemical interactions in the adsorption process. These results confirm the influence of selective COF functionalization on adsorption processes and the role of functional groups on the adsorption selectivity, thus clearly demonstrating the potential of this new class of materials in the efficient and selective capture and removal of pollutants in aqueous solutions.This work was funded by the Coimbra Chemistry Centre (CQC), which is supported by the Fundação para a Ciência e a Tecnologia (FCT), Portugal, through the grants ref. UID/QUI/00313/2020 and ref. UI/BD/150809/2020, co-funded by COMPETE2020-UE

Development of a dextrin-based hydrogel for bone regeneration

[Excerpt] Bone tissue engineering is a very challenging and promising field, which handles with the limitations of bone regenerative capacity and the failure of current orthopedic implants [1]. This work describes the preparation and characterization of an injectable dextrin-based hydrogel (oDex) able to incorporate nanoparticles, cells, biomolecules or Bonelike~ granules [2]. (...

How to integrate sustainability teaching and learning in Higher Education Institutions? From context to action for transformation towards SDGs implementation: a literature review

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Microencapsulation of Lactobacillus paracasei LAFTI® L26 by extrusion in an alginate matrix

Probiotic bacteria are currently used in the development of functional food products, yet sometimes face technological challenges when incorporated in food matrices with more aggressive environments – salt, acid or oxygen concentrations. Encapsulation is an efficient technique to overcome such difficulties since encapsulation microcapsules help in their protection from both the product intrinsic properties and the gastrointestinal tract. Among the many factors influencing encapsulation efficiency, capsule size is an important issue since it can affect the textural and sensorial properties of the food product to which they are added. In this research work the microencapsulation efficiency and stability throughout storage of calcium alginate capsules (produced by extrusion) of Lactobacillus paracasei LAFTI® L26 was studied. Initially, extrusion by coaxial flow was used for encapsulation. Storage in Ringer solution at 4 ºC in a 1:9 (g/mL) racio – and the effect of a protecting agent – lactose, were assessed (samples collected at 0, 3, 5, 7 and 14d). In order to reduce the capsules’ size, extrusion by aerodynamically assisted flow was also tested and two different rupture solutions (sodium citrate 2 %(w/v) and phosphate buffer (0.5 M; pH 7)) were assessed. The capsules obtained via extrusion by coaxial flow presented dimensions superior to 200 µm. The incorporation method was shown to be effective. Suspension of the L. paracasei LAFTI® L26 alginate capsules in Ringer solution and storage at 4 ºC was shown to be a good preservation method and lactose did not present a protective effect. Such encapsulation increased survival of bacteria under storage at 4 ºC for two months (samples collected at 0, 3, 5, 7, 14, 21, 30 and 60d), reducing the decline of viable cell numbers when in comparison with free cells (3 log cycles versus 4 log cycles). The size of the capsules obtained using extrusion by aerodynamically assisted flow was smaller than 100 µm which allows the capsules to be incorporated in food products without a negative sensorial perception. The encapsulation method was also shown to be effective and no difference between rupture solutions was observed.info:eu-repo/semantics/publishedVersio