RESUMO
Sulfated glycosaminoglycans (GAGs) can direct cellular processes by interacting with proteins of the extracellular matrix (ECM). In this study we characterize the interaction profiles of chemically sulfated hyaluronan (HA) and chondroitin sulfate (CS) derivatives with bone morphogenetic protein-2 (BMP-2) and investigate their relevance for complex formation with the receptor BMPR-IA. These goals were addressed by surface plasmon resonance (SPR) and ELISA in combination with molecular modeling and dynamics simulation. We found not only the interaction of BMP-2 with GAGs to be dependent on the type and sulfation of GAGs but also BMP-2/GAG/BMPR-IA complex formation. The conformational plasticity of the BMP-2 N-termini plays a key role in the structural and thermodynamic characteristics of the BMP-2/GAG/BMPR-IA system. Hence we propose a model that provides direct insights into the importance of the structural and dynamical properties of the BMP-2/BMPR-IA system for its regulation by sulfated GAGs, in which structural asymmetry plays a key role.
Assuntos
Proteína Morfogenética Óssea 2/química , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/química , Glicosaminoglicanos/química , Materiais Biocompatíveis/química , Técnicas Biossensoriais , Sulfatos de Condroitina/química , Biologia Computacional , Matriz Extracelular/química , Humanos , Ácido Hialurônico/química , Conformação Proteica , Termodinâmica , Engenharia TecidualRESUMO
Dental implants are an established therapy for oral rehabilitation. High success rates are achieved in healthy bone, however, these rates decrease in compromised host bone. Coating of dental implants with components of the extracellular matrix is a promising approach to enhance osseointegration in compromised peri-implant bone. Dental titanium implants were coated with an artificial extracellular matrix (aECM) consisting of collagen type I and either one of two regioselectively low sulfated hyaluronan (sHA) derivatives (coll/sHA1Δ6s and coll/sHA1) and compared to commercial pure titanium implants (control). After extraction of the premolar teeth, 36 implants were inserted into the maxilla of 6 miniature pigs (6 implants per maxilla). The healing periods were 4 and 8 weeks, respectively. After animal sacrifice, the samples were evaluated histomorphologically and histomorphometrically. All surface states led to a sufficient implant osseointegration after 4 and 8 weeks. Inflammatory or foreign body reactions could not be observed. After 4 weeks of healing, implants coated with coll/sHA1Δ6s showed the highest bone implant contact (BIC; coll/sHA1Δ6s: 45.4%; coll/sHA1: 42.2%; control: 42.3%). After 8 weeks, a decrease of BIC could be observed for coll/sHA1Δ6s and controls (coll/sHA1Δ6s: 37.3%; control: 31.7 %). For implants coated with coll/sHA1, the bone implant contact increased (coll/sHA1: 50.8%). Statistically significant differences could not be observed. Within the limits of the current study, aECM coatings containing low sHA increase peri-implant bone formation around dental implants in maxillary bone compared to controls in the early healing period.
Assuntos
Materiais Revestidos Biocompatíveis/química , Colágeno/química , Implantes Dentários , Ácido Hialurônico/análogos & derivados , Osseointegração , Animais , Feminino , Humanos , Ácido Hialurônico/química , Teste de Materiais , Maxila/anatomia & histologia , Maxila/cirurgia , Modelos Animais , Suínos , Porco Miniatura , Titânio/químicaRESUMO
Sulfated glycosaminoglycans (GAGs) are principal elements of the extracellular matrix, where they are involved in a plethora of signaling pathways mainly via interactions with diverse proteins such as growth factors and cytokines. However, the mechanisms that drive these interactions are not yet clear, mostly because of the difficulty to access large quantities of homogeneously sulfated natural GAGs. In this work, GAG mimics are synthesized from readily available alginate with different degrees of sulfation (DS, from 0.8 to 2.6) by simple process. The effect of the DS is determined on the binding of basic fibroblast growth factor (FGF-2). The enzyme-linked immunosorbent assay demonstrates that the binding of FGF-2 is significantly greater for alginates with high DS as compared to unmodified and low sulfated analogs. These results are further applied to engineer FGF-2-loaded substrates for stem cell culturing using the layer-by-layer approach. All films support the attachment and growth of adipose derived stem cells (ADSCs). Noteworthy, highly sulfated alginates maintain the stemness of the ADSCs that exhibit remarkably long filopodia. These results can be exploited in the engineering of novel substrates that induce targeted cell behavior via controlled protein delivery and for tissue engineering constructs applicable in various regenerative approaches.
RESUMO
Innovative biomaterial-based concepts are required to improve wound healing of damaged vascularized tissues especially in elderly multimorbid patients. To develop functional hydrogels as 3D cellular microenvironments and as carrier or scavenging systems, e.g., for mediator proteins or proinflammatory factors, collagen fibrils are embedded into a network of photo-crosslinked acrylated hyaluronan (HA), chondroitin sulfate (CS), or sulfated HA (sHA). After lyophilization, the gels show a porous structure and an improved stability against degradation via hyaluronidase. Gels with CS and sHA bind significantly more lysozyme than HA/collagen gels and retard its release. The proliferation and metabolic activity of endothelial cells are significantly increased on sHA gels compared to CS- or only HA-containing hydrogels. These findings highlight the potential of HA/collagen hydrogels with sulfated glycosaminoglycans to tune the protein binding and release behavior and to directly modulate cellular response. This can be easily translated into biomimetic biomaterials with defined properties to stimulate wound healing.
Assuntos
Colágeno/farmacologia , Células Endoteliais/citologia , Ácido Hialurônico/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Sulfatos/farmacologia , Acrilatos/química , Animais , Bovinos , Proliferação de Células/efeitos dos fármacos , Forma Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glicosaminoglicanos/química , Humanos , Hialuronoglucosaminidase/metabolismo , Hidrogéis/síntese química , Hidrogéis/química , Muramidase/metabolismo , Ligação Proteica/efeitos dos fármacos , Ratos , Sus scrofaRESUMO
Bioprinting is an emerging technology in the field of tissue engineering as it allows the precise positioning of biologically relevant materials in 3D, which more resembles the native tissue in our body than current homogenous, bulk approaches. There is however a lack of materials to be used with this technology and materials such as the block copolymer Pluronic have good printing properties but do not allow long-term cell culture. Here we present an approach called nanostructuring to increase the biocompatibility of Pluronic gels at printable concentrations. By mixing acrylated with unmodified Pluronic F127 it was possible to maintain the excellent printing properties of Pluronic and to create stable gels via UV crosslinking. By subsequent elution of the unmodified Pluronic from the crosslinked network we were able to increase the cell viability of encapsulated chondrocytes at day 14 from 62% for a pure acrylated Pluronic hydrogel to 86% for a nanostructured hydrogel. The mixed Pluronic gels also showed good printability when cells where included in the bioink. The nanostructured gels were, with a compressive modulus of 1.42 kPa, mechanically weak, but we were able to increase the mechanical properties by the addition of methacrylated hyaluronic acid. Our nanostructuring approach enables Pluronic hydrogels to have the desired set of properties in all stages of the bioprinting process.
Assuntos
Materiais Biocompatíveis/química , Bioimpressão/métodos , Hidrogéis/química , Nanoestruturas/química , Poloxâmero/química , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/farmacologia , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ácido Hialurônico , Impressão TridimensionalRESUMO
Layer-by-layer bioprinting is a logical choice for the fabrication of stratified tissues like articular cartilage. Printing of viable organ replacements, however, is dependent on bioinks with appropriate rheological and cytocompatible properties. In cartilage engineering, photocrosslinkable glycosaminoglycan-based hydrogels are chondrogenic, but alone have generally poor printing properties. By blending the thermoresponsive polymer poly(N-isopropylacrylamide) grafted hyaluronan (HA-pNIPAAM) with methacrylated hyaluronan (HAMA), high-resolution scaffolds with good viability were printed. HA-pNIPAAM provided fast gelation and immediate post-printing structural fidelity, while HAMA ensured long-term mechanical stability upon photocrosslinking. The bioink was evaluated for rheological properties, swelling behavior, printability and biocompatibility of encapsulated bovine chondrocytes. Elution of HA-pNIPAAM from the scaffold was necessary to obtain good viability. HA-pNIPAAM can therefore be used to support extrusion of a range of biopolymers which undergo tandem gelation, thereby facilitating the printing of cell-laden, stratified cartilage constructs with zonally varying composition and stiffness.
Assuntos
Resinas Acrílicas/química , Cartilagem/química , Condrócitos/metabolismo , Ácido Hialurônico/química , Impressão Tridimensional , Alicerces Teciduais/química , Animais , Bovinos , Células Cultivadas , Condrócitos/citologia , Teste de Materiais/métodosRESUMO
PURPOSE: The aim of this work was to investigate the reaction mechanism of electron-beam generated macroporous dextran cryogels by quantum chemical calculation and electron paramagnetic resonance measurements. METHODS: Electron-beam radiation was used to initiate the cross-linking reaction of methacrylated dextran in semifrozen aqueous solutions. The pore morphology of the resulting cryogels was visualized by scanning electron microscopy. Quantum chemical calculations and electron paramagnetic resonance studies provided information on the most probable reaction pathway and the chain growth radicals. RESULTS: The most probable reaction pathway was a ring opening reaction and the addition of a C-atom to the double-bond of the methacrylated dextran molecule. CONCLUSIONS: First detailed quantum chemical calculation on the reaction mechanism of electron-beam initiated cross-linking reaction of methacrylated dextran are presented.
Assuntos
Dextranos/química , Dextranos/efeitos da radiação , Metacrilatos/química , Metacrilatos/efeitos da radiação , Criogéis , Espectroscopia de Ressonância de Spin Eletrônica , Elétrons , Microscopia Eletrônica de Varredura , Modelos Químicos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Porosidade , Teoria QuânticaRESUMO
Glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are important, natural polysaccharides which occur in biological (connective) tissues and have various biotechnological and medical applications. Additionally, there is increasing evidence that chemically (over)sulfated GAGs possess promising properties and are useful as implant coatings. Unfortunately, a detailed characterization of these GAGs is challenging: although mass spectrometry (MS) is one of the most powerful tools to elucidate the structures of (poly)saccharides, MS is not applicable to high mass polysaccharides, but characteristic oligosaccharides are needed. These oligosaccharides are normally generated by enzymatic digestion. However, chemically modified (particularly sulfated) GAGs are extremely refractive to enzymatic digestion. This study focuses on the investigation of the digestibility of GAGs with different degrees of sulfation by bovine testicular hyaluronidase (BTH). It will be shown by using an adapted spectrophotometric assay that all investigated GAGs can be basically digested if the reaction conditions are carefully adjusted. However, the oligosaccharide yield correlates reciprocally with the number of sulfate residues per polymer repeating unit. Finally, matrix-laser desorption and ionization (MALDI) MS will be used to study the released oligosaccharides and their sulfation patterns.
Assuntos
Ácido Hialurônico/metabolismo , Hialuronoglucosaminidase/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Sulfatos/metabolismo , Testículo/enzimologia , Absorção Fisico-Química , Animais , Bovinos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Masculino , Peso Molecular , Espectrofotometria UltravioletaRESUMO
This study focuses on the development of novel biocompatible macroporous cryogels by electron-beam assisted free-radical crosslinking reaction of polymerizable dextran and hyaluronan derivatives. As a main advantage this straightforward approach provides highly pure materials of high porosity without using additional crosslinkers or initiators. The cryogels were characterized with regard to their morphology and their basic properties including thermal and mechanical characteristics, and swellability. It was found that the applied irradiation dose and the chemical composition strongly influence the material properties of the resulting cryogels. Preliminary cytotoxicity tests illustrate the excellent in vitro-cytocompatibility of the fabricated cryogels making them especially attractive as matrices in tissue regeneration procedures.
Assuntos
Materiais Biocompatíveis/síntese química , Criogéis/síntese química , Criogéis/toxicidade , Dextranos/química , Dextranos/toxicidade , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Células 3T3 , Animais , Materiais Biocompatíveis/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Dextranos/efeitos da radiação , Módulo de Elasticidade , Elétrons , Dureza , Ácido Hialurônico/efeitos da radiação , Teste de Materiais , Camundongos , Condutividade TérmicaRESUMO
Sulfated glycosaminoglycans (GAG) are components of the bone marrow stem cell niche and to a minor extent of mature bone tissue with important functions in regulating stem cell lineage commitment and differentiation. We anticipated that artificial extracellular matrices (aECM) composed of collagen I and synthetically oversulfated GAG derivatives affect preferentially the differentiation of osteoblast-precursor cells and early osteoblasts. A set of gradually sulfated chondroitin sulfate and hyaluronan derivatives was used for the preparation of aECM. All these matrices were analysed with human bone marrow stromal cells to identify the most potent aECM and to determine the influence of the degree and position of sulfate groups and the kind of disaccharide units on the osteogenic differentiation. Oversulfated GAG derivatives with a sulfate group at the C-6 position of the N-acetylglycosamine revealed the most pronounced proosteogenic effect as determined by tissue nonspecific alkaline phosphatase activity and calcium deposition. A subset of the aECM was further analysed with different primary osteoblasts and cell lines reflecting different maturation stages to test whether the effect of sulfated GAG derivatives depends on the maturation status of the cells. It was shown that the proosteogenic effect of aECM was most prominent in early osteoblasts.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Glicosaminoglicanos/farmacologia , Osteoblastos/citologia , Células-Tronco/citologia , Adulto , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/metabolismo , Bovinos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Feminino , Glicosaminoglicanos/química , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Ratos Wistar , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxide-pyridine complex (SO3/pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by ß1 blocking antibodies (p=0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ.
Assuntos
Alginatos/química , Cartilagem Articular/citologia , Cartilagem Articular/crescimento & desenvolvimento , Condrócitos/citologia , Condrócitos/fisiologia , Condrogênese/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Animais , Técnicas de Cultura Celular por Lotes/instrumentação , Técnicas de Cultura Celular por Lotes/métodos , Materiais Biomiméticos/síntese química , Bovinos , Diferenciação Celular , Proliferação de Células/fisiologia , Células Cultivadas , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Sulfatos/química , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
Glycosaminoglycans and its derivatives have gained increasing attention for the fabrication of hydrogels usable in biomedicine. Starting from high molecular weight hyaluronan, a natural glycosaminoglycan that forms a mayor component of the native extracellular matrix, we present an efficient phase-transfer-based synthesis for low molecular weight hyaluronan acrylates with a tailored degree of substitution (DS) ranging up to DS values of 1.7. The ability of these compounds to form dimensionally stable hydrogels was proven using different photo-initiator systems.
Assuntos
Acrilatos/química , Ácido Hialurônico/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Reagentes de Ligações Cruzadas/química , Ácido Hialurônico/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Luz , Teste de Materiais , Peso Molecular , Transição de Fase , Polissacarídeos Bacterianos/química , Streptococcus/químicaRESUMO
Bioprinting is an emerging technology that has its origins in the rapid prototyping industry. The different printing processes can be divided into contact bioprinting(1-4) (extrusion, dip pen and soft lithography), contactless bioprinting(5-7) (laser forward transfer, ink-jet deposition) and laser based techniques such as two photon photopolymerization(8). It can be used for many applications such as tissue engineering(9-13), biosensor microfabrication(14-16) and as a tool to answer basic biological questions such as influences of co-culturing of different cell types(17). Unlike common photolithographic or soft-lithographic methods, extrusion bioprinting has the advantage that it does not require a separate mask or stamp. Using CAD software, the design of the structure can quickly be changed and adjusted according to the requirements of the operator. This makes bioprinting more flexible than lithography-based approaches. Here we demonstrate the printing of a sacrificial mold to create a multi-material 3D structure using an array of pillars within a hydrogel as an example. These pillars could represent hollow structures for a vascular network or the tubes within a nerve guide conduit. The material chosen for the sacrificial mold was poloxamer 407, a thermoresponsive polymer with excellent printing properties which is liquid at 4 °C and a solid above its gelation temperature ~20 °C for 24.5% w/v solutions(18). This property allows the poloxamer-based sacrificial mold to be eluted on demand and has advantages over the slow dissolution of a solid material especially for narrow geometries. Poloxamer was printed on microscope glass slides to create the sacrificial mold. Agarose was pipetted into the mold and cooled until gelation. After elution of the poloxamer in ice cold water, the voids in the agarose mold were filled with alginate methacrylate spiked with FITC labeled fibrinogen. The filled voids were then cross-linked with UV and the construct was imaged with an epi-fluorescence microscope.
Assuntos
Bioimpressão/métodos , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Hidrogéis/química , Alginatos/química , Bioimpressão/instrumentação , Dermoscopia , Fibrinogênio/química , Fluoresceína-5-Isotiocianato/química , Temperatura Alta , Metacrilatos/química , Poloxâmero/química , Sefarose/químicaRESUMO
Glycosaminoglycans (GAGs) in the extracellular matrix (ECM) have multiple functions in tissues including providing support, mediating cell division and differentiation, and taking part in important interactions with proteins, e.g. growth factors. Studying GAG related interactions is inherently difficult and requires suitable interaction platforms. We show two strategies to covalently couple the GAG chondroitin sulfate (CS) to supported lipid bilayers (SLBs), either by (a) activating carboxy-functionalized phospholipids in the lipid bilayer, followed by the addition of hydrazide-functionalized CS, or by (b) activating naturally occurring carboxyl groups on CS prior to addition to an amino-functionalized SLB. Bilayer formation and subsequent immobilization was followed in real-time using the Quartz Crystal Microbalance with Dissipation monitoring, a technique that provides unique information when studying highly hydrated molecular films. The two strategies yielded thin CS films (in the nanometer range) with similar viscoelastic properties. Fluidity of the lipid bilayer was retained when CS was coupled. The application of the CS interaction platform was exemplified for type I collagen and the bone inducing growth factor bone morphogenetic protein-2 (BMP-2). The addition of collagen to immoblized CS resulted in soft layers whereas layers formed by addition of BMP-2 were denser, independent on the immobilization strategy used.
Assuntos
Proteína Morfogenética Óssea 2/química , Sulfatos de Condroitina/química , Colágeno Tipo I/química , Proteínas Imobilizadas/química , Bicamadas Lipídicas/química , Fosfolipídeos/química , Elasticidade , HumanosRESUMO
Molecular interactions involving glycosaminoglycans (GAGs) are important for biological processes in the extracellular matrix (ECM) and at cell surfaces, and also in biotechnological applications. Enzymes in the ECM constantly modulate the molecular structure and the amount of GAGs in our tissues. Specifically, the changeable sulfation patterns of many GAGs are expected to be important in interactions with proteins. Biotinylation is a convenient method for immobilizing molecules to surfaces. When studying interactions at the molecular, cell and tissue level, the native properties of the immobilized molecule, i.e. its biofunctionality, need to be retained upon immobilization. Here, the GAGs hyaluronan (HA) and chondroitin sulfate (CS), and synthetically sulfated derivatives of the two, were immobilized using biotin-streptavidin binding. The degree of biotinylation and the placement of biotin groups (end-on/side-on) were varied. The introduction of biotin groups could have unwanted effects on the studied molecule, but this aspect that is not always straightforward to evaluate. Hyaluronidase, an enzyme that degrades HA and CS in the ECM, was investigated as a probe to evaluate the biofunctionality of the immobilized GAGs, using both quartz crystal microbalance and high-performance liquid chromatography. Our results showed that end-on biotinylated HA was efficiently degraded by hyaluronidase, whereas already a low degree of side-on biotinylation destroyed the degrading ability of the enzyme. Synthetically introduced sulfate groups also had this effect. Hence hyaluronidase degradation is a cheap and easy way to investigate how molecular function is influenced by the introduced functional groups. Binding experiments with the proteoglycan aggrecan emphasized the influence of protein size and surface orientation of the GAGs for in-depth studies of GAG behavior.
Assuntos
Agrecanas/química , Sulfatos de Condroitina/química , Ácido Hialurônico/química , Hialuronoglucosaminidase/química , Biotinilação , Ativação EnzimáticaRESUMO
9-Aminoacridine was established as a matrix for the detection of neutral oligosaccharides in negative ion mode matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. Sodium iodide proved to be a useful additive inducing formation of stable iodide adducts of the analytes, in particular for oligosaccharides with a degree of polymerisation (DP) of three and higher. Lower oligomers (DP <3) and monosaccharides show more stable adducts with chloride ions. After optimisation of the sample preparation procedure, limits of quantitation were determined for alpha-cyclodextrin and cellopentaose at 7 and 13 pmol, respectively, with a linear detector response over two concentration orders. The iodide additive could be successfully employed on MALDI-TOF mass spectrometers with vacuum and atmospheric pressure ion sources. The value of the new method to solve biological problems has been demonstrated by the analysis of a mixture of beta-glucane elicitors isolated from the cell walls of Phytophthora sojae.
Assuntos
Aminacrina/química , Cloretos/química , Oligossacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Pressão Atmosférica , Parede Celular/química , Oligossacarídeos/análise , Phytophthora/química , alfa-Ciclodextrinas/análise , alfa-Ciclodextrinas/química , beta-Glucanas/químicaRESUMO
The trinuclear copper(II) complexes ([CuL1)(mu-ac)Cu(mu-ac)CuL1) (1) and ([CuL2)(mu-ac)Cu(mu-ac)CuL2) (2) of the tridentate aminosaccharide-derived Schiff-base ligands H2L1 [6-N-(salicylidene)amino-6-deoxy-1,2,3-tri-O-methyl-alpha-D-glucopyranoside] and H2L2 [6-N-(3,5-di-tert-butylsalicylidene)amino-6-deoxy-1,2,3-tri-O-methyl-alpha-D-glucopyranoside] were synthesized and structurally characterized. The trinuclear complex units can be described as two terminal copper-ligand moieties bridged by a central copper acetate moiety, with the Cu centers arranged in a triangular fashion. IR and UV/vis spectroscopic studies strongly indicate that the trinuclear structure is maintained in a methanolic solution. The temperature dependence of the magnetic susceptibility of both complexes shows a moderate antiferromagnetic coupling and can be well interpreted by applying a symmetric Cua-Cub-Cua' model with linear spin topology. The fit of the magnetic data affords coupling constants J of -34 and -24 cm(-1) for 1 and 2, respectively [H = -J(SaSb + SbSa')]. For mu-alkoxo-mu-acetato-bridged copper(II) complexes with a large dihedral angle between the adjacent coordination planes, as found in 1 and 2, such an antiferromagnetic coupling is unusual. However, density functional theory calculations of 2 using BP86, B3LYP*, and B3LYP density functionals confirmed a symmetric doublet ground state.