Biodegradable Thermogels by Loh Xian Jun;Young David James; & David James Young

Author:Loh, Xian Jun;Young, David James; & David James Young
Language: eng
Format: epub
ISBN: 9781788015394
Publisher: Book Network Int'l Limited trading as NBN International (NBNi)
Published: 2018-09-11T16:00:00+00:00

Figure 5.4 Simplified chemical structure of chitosan.

Chitosan is insoluble in water at physiological pH, but becomes soluble below a pH of 6.5, when -NH2 groups are protonated.11 Chitosan solutions gel in the presence of polyol salts at higher pH values. β-Glycerophosphate (β-GP) is known to induce a sol-to-gel transition in chitosan solutions at physiological pH and temperature.12 A further advantage of chitosan for tissue engineering is its intrinsic antibacterial activity and low immunogenicity.11,12

The mechanism of gelation was first proposed by Chenite and coworkers in the early 2000s.13,14 Adding β-GP salt to the acidic chitosan solution increases the pH to a physiological value (6.8-7.2), while maintaining the solubility of chitosan in water. The thermogelling behaviour of chitosan/β-GP water solutions originates from increasing hydrophobic interactions between chitosan macromolecules at higher temperatures.13 At low temperatures, chitosan aggregation is prevented by the strong interaction with water molecules. Heating increases the hydrophobic interactions between chitosan chains. This is mediated by the presence of β-GP, which masks the positive charge of chitosan amine groups, due to the electrostatic interaction with its own phosphate moieties.14 The electrostatic repulsion between positively charged chitosan chains is effectively reduced.15 Noteworthy is that β-GP does not take part in the physical cross-linking of the chitosan hydrogel, as it can be easily washed out.14 Wang et al.12 developed a chitosan and collagen type I composite thermogelling scaffold for bone tissue engineering. β-GP was chosen as the gelling agent, as it induces a sol-to-gel transition in chitosan and the authors hypothesised it would induce reconstruction of collagen fibrils by neutralising the acidic collagen type I solution. They successfully built composite scaffolds by increasing the solution temperature to 37 °C. Wang and colleagues reported Young's moduli of ≈18 kPa for chitin/collagen ratios of 65/35 and 25/75. Pore sizes in the scaffold ranged from 1 μm to 4 μm. The authors incorporated human bone marrow stem cells (hBMSCs) to assess cell viability, osteogenic differentiation, cytotoxic effects and further biochemical assays. They associated the presence of collagen in the scaffold with increased cell spreading and proliferation as well as with improved scaffold stiffness. In turn, chitosan was associated with increased osteogenic differentiation. The authors also reported a cytotoxic effect of β-GP, as it was found to inhibit cell metabolic activity as soon as 4 h after gelation. Washing the formed gel effectively removed excess salt, but this precludes in situ gel formation. Moreira et al.16 also reported chitosan/collagen composite thermogelling scaffolds for bone tissue engineering using β-GP as the gelling agent. They investigated the incorporation of bioactive glass (BG) nanoparticles into the matrix as a method for promoting the formation of hydroxyapatite (HA), which is characteristic of mineralised bone tissue. They reported improved mechanical properties of chitosan-collagen composites compared to pure chitosan. The G′ value increased from an average of 6.56 Pa to an average of 9.11 Pa (39% increase in stiffness). The incorporation of BG nanoparticles further increased the G′ value to 12.77 Pa average (95% increase in stiffness compared to pure chitosan). The authors reported a sol-to-gel transition temperature of 37±2 °C for the composite scaffold.

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