Ionically-crosslinked carboxymethyl chitosan scaffolds by additive manufacturing for antimicrobial wound dressing applications.

Chitosan chemical functionalization is a powerful tool to provide novel materials for additive manufacturing strategies. The main aim of this study was the employment of computer-aided wet spinning (CAWS) for the first time to design and fabricate carboxymethyl chitosan (CMCS) scaffolds. For this purpose, the synthesis of a chitosan derivative with a high degree of O-substitution (1.07) and water soluble in a large pH range allowed the fabrication of scaffolds with a 3D interconnected porous structure. In particular, the developed scaffolds were composed of CMCS fibers with a small diameter (< 60 µm) and a hollow structure due to a fast non solvent-induced coagulation. Zn2+ ionotropic crosslinking endowed the CMCS scaffolds with stability in aqueous solutions, pH-sensitive water uptake capability, and antimicrobial activity against Escherichia coli and Staphylococcus aureus. In addition, post-printing functionalization through collagen grafting resulted in a decreased stiffness (1.6 ± 0.3 kPa) and a higher elongation at break (101 ± 9 %) of CMCS scaffolds, as well as in their improved ability to support in vitro fibroblast viability and wound healing process. The obtained results encourage therefore further investigation of the developed scaffolds as antimicrobial wound dressing hydrogels for skin regeneration.

Wet-Spun Chitosan-Sodium Caseinate Fibers for Biomedicine: From Spinning Process to Physical Properties.

We designed and characterized chitosan-caseinate fibers processed through wet spinning for biomedical applications such as drug delivery from knitted medical devices. Sodium caseinate was either incorporated directly into the chitosan dope or allowed to diffuse into the chitosan hydrogel from a coagulation bath containing sodium caseinate and sodium hydroxide (NaOH). The latter route, where caseinate was incorporated in the neutralization bath, produced fibers with better mechanical properties for textile applications than those formed by the chitosan-caseinate mixed collodion route. The latter processing method consists of enriching a pre-formed chitosan hydrogel with caseinate, preserving the structure of the semicrystalline hydrogel without drastically affecting interactions involved in the chitosan self-assembly. Thus, dried fibers, after coagulation in a NaOH/sodium caseinate aqueous bath, exhibited preserved ultimate mechanical properties. The crystallinity ratio of chitosan was not significantly impacted by the presence of caseinate. However, when caseinate was incorporated into the chitosan dope, chitosan-caseinate fibers exhibited lower ultimate mechanical properties, possibly due to a lower entanglement density in the amorphous phase of the chitosan matrix. A standpoint is to optimize the chitosan-caseinate composition ratio and processing route to find a good compromise between the preservation of fiber mechanical properties and appropriate fiber composition for potential application in drug release.

Chitosan Based Self-Assembled Nanoparticles in Drug Delivery.

Chitosan is a cationic polysaccharide that is usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive, and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures, and illustrates the state of the art of their application in drug delivery.

Thermosensitive macroporous cryogels functionalized with bioactive chitosan/bemiparin nanoparticles.

Thermosensitive macroporous scaffolds of poly(N-isopropylacrylamide) (polyNIPA) loaded with chitosan/bemiparin nanoparticles are prepared by the free radical polymerization in cryogenic conditions. Chitosan/bemiparin nanoparticles of 102 ± 6.5 nm diameter are prepared by complex coacervation and loaded into polyNIPA cryogels. SEM image reveal the highly porous structure of cryogels and the integration of nanoparticles into the macroporous system. Volume phase transition temperature (VPT) and total freezing water content of cryogels are established by differential scanning calorimetry, and their porosity is determined by image-NMR. Swelling of cryogels (above and below the VPT) is highly dependent on nanoparticles concentration. In vitro release profile of bemiparin from cryogel is highly modulated by the presence of chitosan. Bemiparin released from nanoparticles preserves its biological activity, as shown by the BaF32 cell proliferation assay. Cryogels are not cytotoxic for the human fibroblast cells and present excellent properties for application on tissue engineering and controlled release of heparin.