New Biomedical Polymer Materials Synthesis, Structural Characterization And Performance Studies

Currently, biomedical polymer materials are internationally a very stirring cutting-edge research in the organic polymer chemistry and material discipines, and widely used in diagnosis and treatment, and replacing or repairing of organisms, and the synthesis or regeneration of damaged tissues and organs, having the function of extending life, improving patient survival quality. Especially those biomedical materials such as environmental sensitivity/amphiphilic block copolymers and hydrogels have attracted extensive attention as the drug control release and gene therapy vectors in recent years. How to increase the stability and targeting of block polymer micelles in the blood circulation process, and thus to accomplish the sustained drug release and improve the drug availability, including enhancing the swelling and mechanical strength of hydrogels is of vital importance in the development of biomedical polymer materials. On the other hand, since the biological membrane surface and hemal wall endothelial organization have characteristic microphase separation structure, the studies on relationship among the phase separation, mechanical properties, biocompatibility and micellar stability is a very meaningful work for further examining and meadiating biomedical properties. In view of these descriptions, this dissertation is concerned with the following development to tackle several crucial challenges.1) A novel double brush-shaped block copolymer was synthesized via an atom transfer radical polymerization (ATRP) route, with amphiphilic polyacrylate-b-poly(ethylene glycol)-b-polyacrylate copolymer (PA-b-PEG-b-PA) as a backbone and thermosensitive poly(N-isopropylacrylamide)(PNIPAM) long side chains at both ends of the PEG as brushes, and the structure was confirmed by FTIR,1H NMR and SEC. The thermosensitive self-assembly behavior was examined via UV-vis, TEM, DLS and surface tension measurements, etc. The self-assembled micelles, with low critical solution temperatures (LCST) of34-38℃, form irregular fusiform and/or spherical morphologies with single, double and petaling cores in aqueous solution at room temperature, with broad size distribution, while above the LCST the micelles took on more regular and smooth spherical shapes with narrow and homogeneous size, and diameter ranges from45to100nm. The micelle exhibits high stabilities even in simulated physiological media, with critical micellization concentration (CMC) below 5.50mg L-1. The cytotoxicity was investigated by MTT assays to elucidate the application potential of the as-prepared block polymer brushes as drug controlled release vehicles.2) A series of polyurethane (PU) copolymers with designable molecular weight between cross-linking dots were synthesized by a coupling reaction route. Their swelling, hydrophilicity, degradation and biocompatibility were inspected and assessed based on different degree of polymerization of PANI and PEG and their component proportion. A FTIR,1H NMR, SEM, GPC and goniometry were used to characterize the structure and surface morphologies of as-synthesized PEG/PANI based PU copolymers, PU residues after degradation and degraded polymers at different time periods of hydrolysis. The thermal properties, aggregate structure and surface microstructure were examined by DSC, WAXD and AFM. Hemolysis, static platelet adhesion, dynamic clotting measurements and MTT assays were adopted to evaluate the hemo-or cyto-compatibility. The experimental results indicated that these polymers exhibit various degrees of micro-phase separation depending on the concentrations and degree of polymerization of PANI, molecular weight of PEG, types of curing agents and chain extenders, which further influence their swelling, hydrophilicity, degradable properties and biological performances in vitro. The incorporation of PANI and PANI*in copolymers led to decreased thermal stabilities, but slower decomposition rates than typical PEG based PUs. The stress-strain tests showed that the as-prepared PU copolymers possess increased tensile strength and modulus, and decreased toughness in comparison with the blank PEG based PU. They are expected to find specific applications in tissue engineering or drug controlled release.3) A novel nanohybrid hydrogel was in situ prepared by means of a free radical cross-linking polymerization route of methacrylic acid in the presence of multi-walled carbon nanotubes (MWCNTs). The structural and morphological characterizations revealed that poly(methacrylic acid) networks (PMAA) closely covered the MWCNTs and a MWCNT-well-dispersed nanohybrid hydrogel was formed. The addition of MWCNTs strikingly improved pH response and mechanical properties, depending on component ratios and particle sizes of MWCNTs as well as cross-linker concentrations. The swelling rate was obviously faster than that of the pure PMAA hydrogel. The hydrophilic nature of polyelectrolytes, the capillarity effect, cation-π interaction, a subtle balance between hydrophobic interaction and hydrogen bonds were adopted to interpret the above swelling behavior. Load transfer to the MWCNTs in the networks played important part in compression mechanical improvements. MTT assays were adopted to evaluate the cyto-compatibility of the developed biomaterials. This smart hydrogel is expected to be used as potential candidate for specific biological applications.4) Silver nanoparticles (AgNPs) with controlled size and size distribution were prepared by an in situ chemical reduction route based on a microreactor template composed of poly(acrylamide-co-N-vinylpyrrolidone)/chitosan semi-interpenetrating network hydrogels, P(AAm-co-NVP)/CS semi-IPN. The characterization of structures and morphologies of the as-fabricated P(AAm-co-NVP)/CS-Ag nanocomposite hydrogels was conducted on FTIR, SEM, TEM, and UV-vis. The effect of various component proportions of the reactants on formation of AgNPs and swelling of the resulting nanocomposite hydrogels was investigated. The experimental results indicated that the Ag grains were uniformly dispersed within P(AAm-co-NVP)/CS hydrogel networks in a spherical shape, and were stabilized by the semi-IPN structure and a complexation and/or electrostatic interaction between Ag+cations and chemical functional groups such as-OH,-CONH2,-NH2or-C=O based on the semi-IPN structure reactor templates. The size of the majority of AgNPs ranges from12to25nm, depending on the three-network templates, the presence of functional groups as well as feed ratios of N-vinylpyrrolidone, acrylamide and chitosan. TGA provides the stability of the resulting nanocomposite hydrogels. The nanocomposite hydrogels demonstrate reduced swelling in comparison with the P(AAm-co-NVP)/CS ones. The kinetics modeling confirms that transport mechanism follows anomalous diffusion mode, and the kinetic parameters vary with the component ratios, and the maximal theoretical water volume S∞is well in agreement with the experimental values.