Modification Of The Thermoplastic Starch And Investigation On Its Application As Biomedical Material

Starch is a kind of high-yield biodegradable natrual polysaccharid. Because of its nontoxicity, biodegradability and nontoxicity of the degradation products, starch is a good candidate in biomedical field. In this paper, based on the the aim of biomedical application, thermoplastic starch was chosen as the main raw material. The ageing and degradation mechanisms of glycerol plasticed thermolplastic starch (GTPS) with high glycerol content were investigated.It seems like that the GTPS dissolve in water easily. Furthermore, the mechanical properties can not maintain when immerged in body fluid. In order to improve the ageing resistent ability, water resistent ability and mechanical properties, a series of modifications methods (co-plasticization, esterification, crosslinking and and blending with other polymers) were carried out.Moreover,in order to satisfy some special clinical application (guide tissue regeneration membrane , injected hydrogel for bone repair), the starch/PVA(SP) film and starch/sodium alginate/nano-hydroxylapatite(SSH) composites were prapared.The structure and properties,in vitro degradation behaviour and biocompatibility of SP films and SSH were investigated.In addition, the biocompatibility of the SSH was evaluated by six in vitro and in vivo biological experiments. The repairing effects on rabbit mandibular bone defect were also researched.The main research content and achievements are shown as follows:(1) The thermoplastic starch with the elastomeric properties was prepared by plasticizing with high glycerol content. The elastomeric property was exhibited when the glycerol content was more than 40% (based on the total weight). The ageing mechanism of the complicated tertiary mixture was investigated under the normal human body temperature (37℃) and a comfortable relative humidity for human being (50 RH %), so as to understand the mechanism of the ageing well and to control it under certain conditions of human body. The degradation mechanism of the GTPS elastomer in simulated body fluid and simulated saliva fluid was firstly investigated. The main results including: high glycerol content is helpful to the formation of the single helix structure, but it is not good for the formation of the double helix structure of B-type. There were no reports focused on the relationship between the single helix structures and ageing before. When the glycerol content was more than 40%, there was only a slight change of the mechanical properties within 54days. The results from all characterizations demonstrated that the high glycerol content can prevent ageing effectively. The degradation process in SBF is typical bulk degradation. The GTPS swelled at first, and then degraded. In SSF, the surface and bulk degradation took place at the same time but the surface degradation played an important role in the first 2 h. The influences of the short-term extractions and the long-term degradation products in SBF were proved to be innocuous, which is very important for GTPS to be applicated in biomedical applications. The quick degradation velocity in SSF made GTPS a promising short-term wound dressing material to deal with the stomatitis in oral.(2) In order to prevent ageing and to promote some other properties, a novel citric acid (CA)-glycerol co-plasticized thermoplastic starch (CGTPS) was prepared by melt blending. The structure and properties was investigated. The novel CGTPS has some new characteristics compared with the traditional glycerol plasticized TPS: namely, partial esterification, low molecular weight, and strong interaction between starch and CA. Partial esterification could have some effect on reducing retrogradation, introducing some new groups onto the starch chains for potential modification, and improving the compatibility with some other polyesters. The decrease in the molecular weight can improve the processing properties, adjust the degradation speed, and improve the diffusion of the CGTPS in the polyesters. Furthermore, the CGTPS can easily be prepared by melt blending in a short time. All of these special properties would make CGTPS a good candidate in environment and biomedical applications. (3) A series of starch / PVA (SP) films with 0.05-0.1mm thickness were cast by solvent method. The application of SP films in guide tissue regenaration (GTR) technology was firstly proposed. The in vitro degradation and biocompatibility of the SP films were investigated. Generally speaking, the SP films possess high hydrophilic properties, flexible, strong and adjustable mechanical properties, suitable degradation rate, and excellent biocompatibility. Within 30 days, the integrity of the SP films kept well. The mechanical properties didn't change so much from 3 to 30 days, and SP films showed excellent mechanical stability both in SBF and SSF. It is also very important for its potential use as GTR membrane. Furthermore, in order to overcome the high water absorptence and quick swelling velosity, The SP films were modificated by adding CA and molded at 140℃. The esterification happened between CA and starch (or PVA) as the function of CA. The esterification and the multi-carboxyl structure of CA may result in chemical cross-linking in the blending system.The esterification occured more easily between the starch and CA than that between the PVA and CA. The residual free CA acted as the plasticizer of the starch and PVA. Compared to the hydroxyl groups on glycerol, the carboxyi groups on CA can form stronger hydrogen bonds between CA and other components. The crosslinking and strong hydrogen bonding enhanced the thermal stability and decreased the water absorbance. The cell Relative Growth Rates of all samples with different CA concentration exceeded 80% after 7 day's incubation. This result demonstrated that there was no significant toxicity on cell's growth when the CA content was less than 20%.(4) The starch/sodium alginate/n-HAP (SSH) rejected hydrogel was prepared by melt blending method. According to the Chinese and international standard, six biological evaluation (cytotoxicity, acute toxicity, haemocompatibility, embed in skin and bone )tests pluse a repairing both sides of rabbit mandibular bone defect were investigated. Results demonstrated that the rate of haemocompatibility is 2.06%, no more different between trail and control in acute toxicity, the grade of cytotoxicity is under 1. In the subcutaneous test, there was only a slight subcutaneous tissue reaction. At the same time, complex with n-HA could lead good repairing result in mandibular bone defect. In the bone implant experiment, no absorptance and destruction phenomenons of bone were observed. The SSH could lead good repairing in mandibular bone defect. The SSH is acceptable biological martial and could be a media in repairing bone defect.