The Degradation Of Three-dimensional Chitosan Material And The Control Of Its Degradation Rate

By an original in-situ precipitation method, our research group has successfully prepared three dimensional chitosan rod with a high bending strength, which has a potential application as biodegradable and bioabsorbable internal fixation nail. In this work, we investigated its degradations in preparation process and application process. For example, the influence of heat treatment at different temperatures in the preparation process on the properties and in-vitro degradation rate of chitosan rod was investigated; the influence of 60Co radiation as a sterilization method on the properties and in-vitro degradation rate of chitosan rod was studied; after the in-vitro degradation mechanism and in-vitro degradation rate of chitosan rod were clarified, in order to make the in-vitro degradation rate match the bone repair rate, several methods were adopted to adjust the in-vitro degradation rate of chitosan rod, including using chitosan raw materials with different deacetylation degrees and complexing chitosan rod with microspheres loaded with lysozyme. I hope the results of this research can provide theoretical basis to the safe applications of chitosan-based bone internal fixation materials in the human body.(1) The chitosan rods were heated at 80～400℃for 2 h. During the heat treatment, the CH2OH group in C-6 of chitosan would be oxidized to aldehyde group, and then react with the free amino group of chitosan, forming an intermolecular crosslinking structure. With the increase of temperature (when the temperature was not higher than 200℃), for the chitosan rod, the solubility decreased, and the thermal stability increased. The bending strength reached maximum at 140℃and was 161.3±4.9 MPa. Compared with the bending strength of chitosan rod without heat treatment, the bending strength of CS-140 increased by 33.1%. Moreover, the heat treatment could decrease the in-vitro degradation rate of chitosan rod.(2) Both the chitosan rods and heated chitosan rods were irradiated at doses from 10 kGy to 200 kGy by 60Co irradiation. In the degradation process induced by 60Co irradiation, the chain-scission reaction was dominant and deamination would also happen. With respect to chitosan rod with no heat treatment, when the irradiation dose increased, the molecular weight kept decreasing, and both the crystallization degree and the bending strength reached their maxima at the dose of 20 kGy. In the in-vitro degradation test, CS-20 kGy and CS-0 kGy displayed similar degradation rate. The results indicated that moderate 60Co irradiation not only could strengthen the chitosan rod, but also would not have obvious effect on the in-vitro degradation rate of chitosan rod.(3) The in-vitro degradations of chitosan rod in PBS and lysozyme/PBS were studied. The enzymatic degradation rate at the first week was higher than that at other weeks. This was because the chitosan residues would hinder the penetration of lysozyme into interior chitosan rod. After degraded in PBS and lysozyme/PBS for 24 weeks, the weight losses of chitosan rods were 4.1% and 7.9% respectively. According to the erosion model proposed by Burkersroda et al., the chitosan rod would undergo bulk erosion both in PBS and lysozyme/PBS.(4) Methods such as N-acetylation, blending and layered compositing were adopted to adjust the in-vitro degradation rate of chitosan rod. The results indicated that chitosan rod with different deacetylation degree had different in-vitro degradation rate. Therefore, by adjusting the deacetylation degree of chitosan, the in-vitro degradation rate of chitosan rod could be controlled. Especially when the deacetylation degree of chitosan was 45.7%, the chitosan rod could be fully degraded.(5) A preliminary study was made on tuning the in-vitro degradation rate of chitosan rod by complexing chitosan rod with microspheres loaded with enzyme. In this paper, a hollow chitosan rod was prepared at first, and then the gelatin microspheres loaded with lysozyme were added in. When the mass ratio between lysozyme and gelatin microspheres was 1:12, the encapsulation ratio and loading ratio were the most suitable, and were 75.9% and 6.3% respectively. In the first 14 days of in-vitro degradation, the degradtion rate of the composite rod was much higher than the pure rod, because the lysozyme was released from the gelatin microspheres and degraded the chitosan jointly with lysozyme in the lysozyme/PBS solution.