Three-dimensional wet-spun microfibrous meshes of a star poly(ε-caprolactone) were developed as potential scaffolds endowed with antimicrobial activity. The in vitro release kinetics of the meshes, under physiological conditions, was initially fast and then a sustained release for more than one month was observed. Cell cultures of a murine pre-osteoblast cell line showed good cell viability and adhesion on the wet-spun star poly(ε-caprolactone) fiber scaffolds. These promising results indicate a potential application of the developed meshes as engineered bone scaffolds with antimicrobial activit

A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue-engineering scaffolds. In this study, the manufacture of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer-controlled wet-spinning system, was investigated. By optimizing the processing parameters, three-dimensional scaffolds with different internal architectures were fabricated, based on a layer-by-layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79-88%, fibre diameter 47-76 µm and pore size 123-789 µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase-inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell-culture experiments employing the MC3T3-E1 murine pre-osteoblast cell line showed good cell proliferation after 21 days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.

No abstract

Combining a tissue engineering scaffold made of a load-bearing polymer with a hydrogel represents a powerful approach to enhancing the functionalities of the resulting biphasic construct, such as its mechanical properties or ability to support cellular colonization. This research activity was aimed at the development of biphasic scaffolds through the combination of an additively manufactured poly( -caprolactone) (PCL) fiber construct and a chitosan/poly( -glutamic acid) polyelectrolyte complex hydrogel. By investigating a set of layered structures made of PCL or PCL/hydroxyapatite composite, biphasic scaffold prototypes with good integration of the two phases at the macroscale and microscale were developed. The biphasic constructs were able to absorb cell culture medium up to 10-fold of their weight, and the combination of the two phases had a significant influence on compressive mechanical properties compared with hydrogel or PCL scaffold alone. In addition, due to the presence of chitosan in the hydrogel phase, biphasic scaffolds exerted a broad-spectrum antibacterial activity. The developed biphasic systems appear well suited for application in periodontal bone regenerative approaches in which a biodegradable porous structure providing mechanical stability and a hydrogel phase functioning as absorbing depot of endogenous proteins are simultaneously required.

The application of additive manufacturing principles to hydrogel processing represents a powerful route to develop porous three-dimensional constructs with a variety of potential biomedical applications, such as scaffolds for tissue engineering and three-dimensional in vitro tissue models. The aim of this study was to develop novel porous hydrogels based on a microstructured polyelectrolyte complex between chitosan and poly(γ-glutamic acid) by applying a computer-aided wet-spinning technique. The developed fabrication process was used to build up three-dimensional porous hydrogels by collecting microstructured layers made of chitosan/poly(γ-glutamic acid) on top of the other. Microstructured polyelectrolyte complex hydrogels were characterized and compared to chitosan/poly(γ-glutamic acid) porous hydrogels with similar composition prepared by conventional freeze-drying technique. Fourier transform infrared analysis confirmed the formation of an electrostatic interaction between the two processed polymers in all the developed chitosan/poly(γ-glutamic acid) hydrogels. The composition of the porous constructs as well as the employed processing techniques had a significant influence on the resulting swelling, thermal, and mechanical properties. In particular, the combination of the ionic interaction between chitosan/poly(γ-glutamic acid) and the defined internal microarchitecture of microstructured polyelectrolyte complex hydrogels provided a significant improvement of the compressive mechanical properties. Preliminary in vitro biological investigations revealed that microstructured polyelectrolyte complex hydrogels were suitable for the adhesion and proliferation of Balb/3T3 clone A31 mouse embryo fibroblasts. The encouraging results in terms of cytocompatibility and stability of the microstructure in aqueous solutions due to the ionic crosslinking suggest the investigation of the developed microstructured polyelectrolyte complex hydrogels as suitable scaffolds for three-dimensional cells’ culture.

Development of a novel in vitro 3D model of pancreas cancer based on microstructured polyelectrolyte complex (mPEC) hydrogel.

Cyclodextrin-grafted polymers are attractive biomaterials that could bring together the host–guest complexing capability of pristine cyclodextrin and the pharmaceutical features of the polymeric backbone. The present paper is aimed at characterizing the potential application of ammonium–chitosan grafted with 2-methyl-β-cyclodextrin (N+-rCh-MCD) as the functional macromolecular complexing agent for the oral administration of the neuropeptide dalargin (DAL). Specific NMR characterization procedures, along with UV and fluorescence techniques, as well as biological in vitro assessments have been performed. The results indicate that N+-rCh-MCD forms water-soluble complexes with DAL, with a prevalent involvement of Tyr or Phe over Leu and Ala residues. The association constant of DAL with the polymeric derivative is one order of magnitude higher than that with the pristine cyclodextrin (Ka: 2600 M−1 and 120 M−1, respectively). Additionally, N+-rCh-MCD shields DAL from enzymatic degradation in gastrointestinal in vitro models with a three-fold time delay, suggesting a future pharmaceutical exploitation of the polymeric derivative. Therefore, the greater affinity of N+-rCh-MCD for DAL and its protective effect against enzymatic hydrolysis can be attributed to the synergistic cooperation between cyclodextrin and the polymer, which is realized only when the former is covalently linked to the latter.

As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption.