Alginate bone scaffolds coated with a bioactive lactose modified chitosan for human dental pulp stem cells proliferation and differentiation.

Bioactive and biodegradable porous scaffolds can hasten the healing of bone defects; moreover, patient stem cells seeded onto scaffolds can enhance the osteoinductive and osteoconductive properties of these biomaterials. In this work, porous alginate/hydroxyapatite scaffolds were functionalized with a bioactive coating of a lactose-modified chitosan (CTL). The highly interconnected porous structure of the scaffold was homogeneously coated with CTL. The scaffolds showed remarkable stability up to 60 days of aging. Human Dental Pulp Stem Cells (hDPSCs) cultured in the presence of CTL diluted in culture medium, showed a slight and negligible increase in terms of proliferation rate; on the contrary, an effect on osteogenic differentiation of the cells was observed as a significant increase in alkaline phosphatase activity. hDPSCs showed higher cell adhesion on CTL-coated scaffolds than on uncoated ones. CTL coating did not affect cell proliferation, but stimulated cell differentiation as shown by alkaline phosphatase activity analysis.

Glycosylated-Chitosan Derivatives: A Systematic Review.

Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this set of engineered polysaccharides finds application in different sectors, spanning from food to the biomedical field. Overcoming chitosan (physical) limitations or grafting biological relevant molecules, to mention a few, represent two cardinal strategies to modify parent biopolymer; thereby, synthetizing high added value polysaccharides. The present review is focused on the introduction of oligosaccharide side chains on the backbone of chitosan. The synthetic aspects and the effect on physical-chemical properties of such modifications are discussed. Finally, examples of potential applications in biomaterials design and drug delivery of these novel modified chitosans are disclosed.

Binary Solutions of Hyaluronan and Lactose-Modified Chitosan: The Influence of Experimental Variables in Assembling Complex Coacervates.

A miscibility study between oppositely charged polyelectrolytes, namely hyaluronic acid and a lactose-modified chitosan, is here reported. Experimental variables such as polymers' weight ratios, pH values, ionic strengths and hyaluronic acid molecular weights were considered. Transmittance analyses demonstrated the mutual solubility of the two biopolymers at a neutral pH. The onset of the liquid-liquid phase separation due to electrostatic interactions between the two polymers was detected at pH 4.5, and it was found to be affected by the overall ionic strength, the modality of mixing and the polymers' weight ratio. Thorough Dynamic Light Scattering (DLS) measurements were performed to check the quality of the formed coacervates by investigating their dimensions, homogeneity and surface charge. The whole DLS results highlighted the influence of the hyaluronic acid molecular weight in affecting coacervates' dispersity and size.

N-isopropyl chitosan. A pH- and thermo-responsive polysaccharide for gel formation.

The present contribution deals with the synthesis and characterization of N-isopropyl chitosan in which the introduction of hydrophobic groups leads to an increased flexibility of the polysaccharide backbone. The isopropyl groups extend the solubility of the modified-chitosan samples and render the modified chitosan a pH- and thermo-sensitive system for hydrogel formation. Indeed, upon varying the pH of the system and/or its temperature within a range compatible with biological applications, a non-reversible sol-gel transition occurs, as determined through extended rheological analyses. The modified chitosan samples show a very good biocompatibility as determined through preliminary viability and cell growth experiments.

Three-Dimensional Bone Substitutes for Oral and Maxillofacial Surgery: Biological and Structural Characterization.

BACKGROUND: Bone substitutes, either from human (autografts and allografts) or animal (xenografts) sources, suffer from inherent drawbacks including limited availability or potential infectivity to name a few. In the last decade, synthetic biomaterials have emerged as a valid alternative for biomedical applications in the field of orthopedic and maxillofacial surgery. In particular, phosphate-based bone substitution materials have exhibited a high biocompatibility due to their chemical similitude with natural hydroxyapatite. Besides the nature of the biomaterial, its porous and interconnected architecture is essential for a correct osseointegration. This performance could be predicted with an extensive characterization of the biomaterial in vitro. METHODS: In this study, we compared the biological, chemical, and structural features of four different commercially available bone substitutes derived from an animal or a synthetic source. To this end, µ-CT and SEM were used to describe the biomaterials structure. Both FTIR and EDS analyses were carried out to provide a chemical characterization. The results obtained by these techniques were correlated with cell adhesion and proliferation of the osteosarcoma MG-63 human cell line cultured in vitro. RESULTS: The findings reported in this paper indicate a significant influence of both the nature and the structure of the biomaterials in cell adhesion and proliferation, which ultimately could affect the clinical performance of the biomaterials. CONCLUSIONS: The four commercially available bone substitutes investigated in this work significantly differed in terms of structural features, which ultimately influenced in vitro cell proliferation and may so affect the clinical performance of the biomaterials.

Complex Coacervates between a Lactose-Modified Chitosan and Hyaluronic Acid as Radical-Scavenging Drug Carriers.

Complex coacervation of two oppositely charged polysaccharides, namely a lactose-modified chitosan (CTL) and hyaluronan (HA), was investigated in this study. Coacervates of the two polysaccharides were prepared by drop-by-drop injection of HA into CTL. Transmittance and dynamic light scattering (DLS) measurements in combination with TEM analyses demonstrated the formation of spheroidal colloids in the nano-/microsize range showing good homogeneity. Strikingly, the presence of 150 mM supporting NaCl did not hamper the colloid formation. Stability studies on selected formulations demonstrated that HA/CTL coacervates were stable up to 3 weeks at 37 °C and behaved as pH-responsive colloids since transition from entangled to disentangled chains was attained for a proper pH range. The possibility of freeze-drying the coacervates for storage purposes and the ability of encapsulating selected payloads were investigated as well, for two values of the fraction of the lactitol side-chain substitution (FL). Finally, biological tests using human neutrophils were undertaken at acidic pH value (pH = 6.0): under such experimental conditions, akin to those frequently occurring in the inflammatory microenvironment, coacervates scavenged reactive oxygen species (ROS) generated by these cells in basal conditions. Given the well documented bioactivity of CTL with respect to chitosan toward cartilage regeneration, these findings point to a possible application of HA/CTL-based colloids as scavenging and bioactive carriers for the delivery of therapeutic molecules at confined inflamed sites such as knee joints.