CHITIN IN THE DEVELOPMENT OF HARD TISSUE SUBSTITUTE MATERIALS

Abstract

Chitin was investigated as a potential bone substitute material. Preliminary consideration for this application involved two major aspects: fabrication methods and interaction with calcium phosphate. Gel-processing routes allow the production of various chitin forms including foams, porous forms and dry plates. The porosity of the freeze-dried chitin gel could be controlled by varying the freezing temperature or chitin gel density, a lower freezing temperature or higher gel density giving smaller pore dimensions. The candidate found that the novel chitin foam obtained via critical-point drying of a chitin gel possessed better physical properties compared to the porous forms obtained by freeze-drying. The candidate further investigated post shape modification to satisfy the different requirements for the surface and bulk properties of chitin based biomedical materials. A carboxymethylation reaction was applied to a variety of chitin forms, resulting in novel products possessing different material properties, a bilayer hydrogel, a reversible, water- swellable gel and a porous, acid-modified chitin template. In addition, post-shape modification can be used to tailor the enzyme susceptibility of chitin hydrogels. Water soluble carboxymethyl-chitin (CM-chitin) and phosphoryl-chitin (P-chitin) were inhibitory towards calcium phosphate formation, as demonstrated by turbidimetry and HA seeded growth experiments. The adsorption affinity of P-chitin onto HA was comparable to that of phosphatidylserine and phosphoserine, leading to a potent inhibitory activity on HA seeded growth. When CM-chitin and P-chitin were insolubilized on porous freeze-dried chitin and incubated in a metastable calcium phosphate solution at pH 7.4, the overall effect on calcium phosphate growth was again inhibitory. The candidate postulates that the inhibitory effect is due to chelation of calcium in a manner which sterically inhibits calcium phosphate formation. The unmodified, freeze-dried chitin surface was highly calcifiable and deposition took the form of a continuous, apatite coating. The candidate obtained a chitin-HA composite by a solution processing method, where HA was simultaneously dispersed with chitin, the chitin-HA blend cast into gels and the gels solvent dried to give composite plates. Inclusion of HA provided no reinforcement, but led instead to a decrease in the maximum tensile stress and tensile modulus of the composites, although the composite retained a high elongation to fracture at high volume fraction of the filler. In conclusion, various forms of chitin with potential use in orthopaedics have been investigated in terms of processing, morphology and mechanical properties. Modification of chitin with acidic residues enhances its degradability and water swellability but is inhibitory in terms of enhancing calcification. High levels of calcification can be achieved by employing freeze-dried chitin as the substrate for mineral deposition.