Beyond the Charge: Interplay of Nanogels' Functional Group and Zeta-Potential for Antifungal Drug Delivery to Human Pathogenic Fungus Aspergillus Fumigatus.

The ubiquitous mold Aspergillus fumigatus (A. fumigatus) is one of the main fungal pathogens causing invasive infections in immunocompromised humans. Conventional antifungal agents exhibit limited efficacy and often cause severe side effects.

Engineering peptide-modified alginate-based bioinks with cell-adhesive properties for biofabrication.

Alginate (ALG) and its oxidised form alginate-dialdehyde (ADA) are highly attractive materials for hydrogels used in 3D bioprinting as well as drop-on-demand (DoD) approaches. However, both polymers need to be modified using cell-adhesive peptide sequences, to obtain bioinks exhibiting promising cell-material interactions. Our study explores the modification of ALG- and ADA-based bioinks with the adhesive peptides YIGSR (derived from laminin), RRETEWA (derived from fibronectin) and IKVAV (derived from laminin) for 3D bioprinting.

Thiol-Ene Clickable Gelatin: A Platform Bioink for Multiple 3D Biofabrication Technologies.

Bioprinting can be defined as the art of combining materials and cells to fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so called bioinks, have to comply with challenging rheological processing demands and rapidly form a stable hydrogel postprinting in a cytocompatible manner. Gelatin is often adopted for this purpose, usually modified with (meth-)acryloyl functionalities for postfabrication curing by free radical photopolymerization, resulting in a hydrogel that is cross-linked via nondegradable polymer chains of uncontrolled length.

Application of Linear and Branched Poly(Ethylene Glycol)-Poly(Lactide) Block Copolymers for the Preparation of Films and Solution Electrospun Meshes.

Poly(ethylene glycol)-poly(lactide) (PEG-PLA) block copolymers are processed to solvent cast films and solution electrospun meshes. The effect of polymer composition, architecture, and number of anchoring points for the plasticizer on swelling, degradation, and mechanical properties of these films and meshes is investigated as potential barrier device for the prevention of peritoneal adhesions. As a result, adequate properties are achieved for the massive films with a longer retention of the plasticizer PEG for star-shaped block copolymers than for the linear triblock copolymers and consequently more endurable mechanical properties during degradation.

Multivalent targeting of AT1 receptors with angiotensin II-functionalized nanoparticles.

The angiotensin II receptor type 1 (AT1R) is a G protein-coupled receptor of paramount significance since it is overexpressed in a number of diseased tissues that are highly attractive for nanoparticle targeting. However, it is also expressed at physiological levels in healthy tissue. Multivalent interactions mediated by multiple AT1R-binding moieties per nanoparticle could promote a high binding avidity to AT1R overexpressing cells and concomitantly spare off-target tissue.

Self-assembling colloidal system for the ocular administration of cyclosporine A.

Purpose: In this study, we developed a self-assembling micellar system to deliver cyclosporine A (CsA) in an aqueous solution to the cornea.

Methods: Two nonionic surfactants of the poly(ethylene glycol)-fatty alcohol ether type (Sympatens AS and Sympatens ACS) were characterized in terms of micelle size, shape, and charge, and their encapsulation efficiency for CsA. In an in situ single dose bioavailability study, the corneal CsA levels were determined in an enucleated porcine eye model.

Developing an in situ nanosuspension: a novel approach towards the efficient administration of poorly soluble drugs at the anterior eye.

With about 50-60 million cases in the US alone, dry eye disease represents a severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a causal therapy. However, CsA is not sufficiently water soluble to be administrated via simple eye drops.

Preparation of well-defined calcium cross-linked alginate films for the prevention of surgical adhesions.

Abdominal adhesions are one of the major problems associated with abdominal surgeries or abdominal trauma. There are many different therapeutic options to prevent these adhesions, for example, the application of barrier films made of biodegradable polymers like alginate. For many application relevant parameters (mechanical stability, elasticity, erosion, and mucoadhesivity of the films), the extent of cross-linking with divalent cations, such as calcium, is essential to obtain alginate films with clinically ideal properties.

Ligand-functionalized nanoparticles target endothelial cells in retinal capillaries after systemic application.

To date, diseases affecting vascular structures in the posterior eye are mostly treated by laser photocoagulation and multiple intraocular injections, procedures that destroy healthy tissue and can cause vision-threatening complications. To overcome these drawbacks, we investigate the feasibility of receptor-mediated nanoparticle targeting to capillary endothelial cells in the retina after i.v.

Kidney podocytes as specific targets for cyclo(RGDfC)-modified nanoparticles.

Renal nanoparticle passage opens the door for targeting new cells like podocytes, which constitute the exterior part of the renal filter. When cyclo(RGDfC)-modified Qdots are tested on isolated primary podocytes for selective binding to the αvβ3 integrin receptor a highly cell- and receptor-specific binding can be observed. In displacement experiments with free cyclo(RGDfC) IC(50) values of 150 nM for αvβ3 integrin over-expressing U87-MG cells and 60 nM for podocytes are measured.

Heterobifunctional poly(ethylene glycol) derivatives for the surface modification of gold nanoparticles toward bone mineral targeting.

Heterobifunctional poly(ethylene glycol)s can be used for many biomedical applications ranging from solubility enhancement of hardly soluble compounds to surface modification of medical devices. In order to modify gold nanoparticles as model particles for drug targeting applications, PEG derivatives are synthesized that possess a high affinity for gold surfaces, namely a thioalkyl function, known to form stable monolayers on gold. Additionally a bisphosphonate function is introduced in the PEG molecule to allow targeting of hydroxyapatite rich tissues, like bone.

Foamed oligo(poly(ethylene glycol)fumarate) hydrogels as versatile prefabricated scaffolds for tissue engineering.

Radically cross-linked hydrogels are frequently used as cell carriers due to their excellent biocompatibility and their tissue-like mechanical properties. Through frequent investigation, PEG-based polymers such as oligo(poly(ethylene glycol)fumarate [OPF] have proven to be especially suitable as cell carriers by encapsulating cells during hydrogel formation. In some cases, NaCl or biodegradable gelatin microparticles were added prior to cross-linking in order to provide space for the proliferating cells, which would otherwise stay embedded in the hydrogel matrix.

G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake.

More selective interactions of nanoparticles with cells would substantially increase their potential for diagnostic and therapeutic applications. Thus, it would not only be highly desirable that nanoparticles can be addressed to any cell with high target specificity and affinity, but that we could unequivocally define whether they rest immobilized on the cell surface as a diagnostic tag, or if they are internalized to serve as a delivery vehicle for drugs. To date no class of targets is known that would allow direction of nanoparticle interactions with cells alternatively into one of these mutually exclusive events.

Biodegradable hydrogels for time-controlled release of tethered peptides or proteins.

Tethering drug substances to a gel network is an effective way of controlling the release kinetics of hydrogel-based drug delivery systems. Here, we report on in situ forming, biodegradable hydrogels that allow for the covalent attachment of peptides or proteins. Hydrogels were prepared by step-growth polymerization of branched poly(ethylene glycol).

Size-dependent release of fluorescent macromolecules and nanoparticles from radically cross-linked hydrogels.

Hydrogels play an important role in drug delivery and tissue engineering applications due to their excellent biocompatibility and their variable mechanical and physical properties, which allow their optimization for many different aspects of the intended use. In this study, we examined the suitability of poly(ethylene glycol) (PEG)-based hydrogels as release systems for nanometer-sized drugs or drug carriers, like nanoparticles, using the radically cross-linkable oligo(poly(ethylene glycol)fumarate) (OPF) together with two cross-linking agents. Different fluorescent nanoparticulate probes with respect to size and physical structure were incorporated in the cross-linked hydrogels, and the obtained release profiles were correlated with the physical properties and the chemical structure of the gels, indicating a strong dependence of the release on the chosen PEG prepolymers.

Ascorbic acid enhances adipogenesis of bone marrow-derived mesenchymal stromal cells.

A prerequisite to successfully engineer cell-based adipose tissue surrogates is the evaluation of in vitro culture conditions that facilitate expansion of primary precursor cells under retention of their adipogenic potential and that enable a large fraction of the heterogeneous cell pool to undergo adipogenesis upon respective stimuli. Ascorbic acid (AA) was reported to enhance differentiation of precursor cells into various mesenchymal cell types. Thus, the aim of the current study was to evaluate the influence of AA on hormonally induced adipogenesis of bone marrow-derived mesenchymal stromal cells (BMSCs) in vitro when supplemented during cell propagation and/or adipogenic differentiation.

In vivo development and long-term survival of engineered adipose tissue depend on in vitro precultivation strategy.

One strategy of adipose tissue engineering is to transplant adipocytes or adipocyte precursor cells in combination with polymeric materials. However, a satisfying formation of fat tissue and its long-term survival still remain major problems. There is increasing evidence that treatment of the cells prior to implantation plays a critical role in the success of adipose tissue growth.

In vitro and in vivo cartilage engineering using a combination of chondrocyte-seeded long-term stable fibrin gels and polycaprolactone-based polyurethane scaffolds.

The use of either a hydrogel or a solid polymeric scaffold alone is often associated with distinct drawbacks in many tissue engineering applications. Therefore, in this study, we investigated the potential of a combination of long-term stable fibrin gels and polyurethane scaffolds for cartilage engineering. Primary bovine chondrocytes were suspended in fibrin gel and subsequently injected into a polycaprolactone-based polyurethane scaffold.

Matrices and scaffolds for protein delivery in tissue engineering.

The tissue engineering of functional tissues depends on the development of suitable scaffolds to support three dimensional cell growth. To improve the properties of the scaffolds, many cell carriers serve dual purposes; in addition to providing cell support, cutting-edge scaffolds biologically interact with adhering and invading cells and effectively guide cellular growth and development by releasing bioactive proteins like growth factors and cytokines. To design controlled release systems for certain applications, it is important to understand the basic principles of protein delivery as well as the stability of each applied biomolecule.

Ascorbic acid modulates proliferation and extracellular matrix accumulation of hyalocytes.

Ascorbic acid is known to influence proliferation and functional properties of several cell types and is therefore widely used in tissue engineering. In this study, the effect of ascorbic acid on the proliferation and functional properties of hyalocytes was evaluated. Hyalocytes were cultured with different amounts of ascorbic acid in classical two-dimensional (2-D) cultures and a three-dimensional (3-D) pellet culture system.

Confocal microscopy for the elucidation of mass transport mechanisms involved in protein release from lipid-based matrices.

Purpose: It was the aim of this study to identify the governing mechanisms during protein release from cylindrical lipid matrices by visualizing mass transport and correlating the data with in vitro dissolution testing.

Materials And Methods: Glyceryl trimyristate cylinders of 2 mm diameter, 2.2 mm height and 7 mg weight were manufactured by compression of a protein-lipid powder mixture prepared by a polyethylene glycol (PEG) co-lyophilization technique.

Customized PEG-derived copolymers for tissue-engineering applications.

PEG-containing copolymers play a prominent role as biomaterials for different applications ranging from drug delivery to tissue engineering. These custom-designed materials offer enormous possibilities to change the overall characteristics of biomaterials by improving their biocompatibility and solubility, as well as their ability to crystallize in polymer blends and to resist protein adsorption. This article demonstrates various principles of PEG-based material design that are applied to fine tune the properties of biomaterials for different tissue engineering applications.

Basic fibroblast growth factor enhances PPARgamma ligand-induced adipogenesis of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are capable of differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and differentiation factors. It is widely acknowledged that basic fibroblast growth factor (bFGF) modulates chondrogenic and osteogenic differentiation of MSCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate on the cellular and molecular level that supplementation of bFGF in different phases of cell culture leads to a strong enhancement of adipogenesis of MSCs, as induced by an adipogenic hormonal cocktail.

Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment.

This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.