Preparation And Application Of Novel Cross-linked Controllable Biodegradable Materials For Bone Repair And Regeneration

Biomaterials applied to bone repair and regeneration should be characterized by their biocompatibility, hydrophilicity and mechanical properties. They are also supposed to degrade at a rate which can match the growth of tissue. Most present researches are focused on three sorts of materials: polyester, polysaccharid and calcium-phosphate. Polyester has outstanding mechanical strength, nevertheless, poor hydrophilicity. It can be improved by introducing hydrophilic chain, which, however, will bring about an evident reduction in molecular weight and mechanical strength. Polysaccharids has the advantage of biocompatibility, while they are difficult to be shaped and be controlled during degradation. Although the defect of high brittleness of pure calcium-phosphate can be made up by the combination with collagen, it is often followed by lower mechanical properties and over-degradation. For these reasons, so far they only have very limited application for clinical purposes.This paper is to discuss a novle kind of biomaterial different from the aforesaid. Biodegradable cross-linker and macromer were employed to construct the molecular backbone, which could ensure the mechanical strength of the material. The incorporation of water-soluble chains into the molecular networks could maintain the hydrophilicity of the material. Also, it played an crucial part in control of the degrading rate.The study began with syntheses of the macromers of poly [D,L-lactide-co-(2-hydroxyethyl methacrylate)] (PLA-HEMA, MC) and the biodegradable cross-linker of poly (lactic acid)- poly (ethylene glycol)(PLA-PEG-PLA) plus terminal groups of vinyl(BC). Both of them were then reacted with vinylpyrrolidone (NVP) and brought forth a series of cross-linked terpolymer, whose physicochemical properties were adjustable due to their ingredient, specifically, hydrophobic MC, amphiphilic BC and hydrophilic NVP. As the molar ratio n(BC)/n(MC)/n(NVP) changed from 1:1:10 to 1:4:30, the surface contact angles varied between 51°and 73°, and the water adsorption between 20％and 110％. PVP chains polymerized with NVP were introduced into the networks, which evidently improved the hydrophilicity of the cross-linked materials and the surface condition for cell adhesion. Furthermore, it proved to be possible that the network associated with PVP entirely degraded. With the hydrolysis of the PLA segment, the kinetic chains (polyacrylate-polymethacrylate-PVP) could readily dissolve into water.In the second step, the biodegradable cross-linker was used to knit networks so as to maintain the mechanical strength. Compared with those traditional processing methods, such as injection molding and freezing drying, the chemical cross-linking technique could contribute to better degradability and mechanical strength, therefore, could meet the clinical requirements better. Tensile strength of the cross-linked terpolymer ranged between 5.29 and 8.27MPa, and elongation at break between 68.5％and 144.7％; Compression modulus of the inorganic matrix/cross-linked terpolymers ranged between 18.6 and 109.8MPa, which were to serve as scaffolds for tissue growing in rabbit radius defeat experiments.Relative length of the molecular chain in the networks were dependent on the n(BC)/n(MC)/n(NVP), and so were the hydrophobic-hydrophilic discrete micro-districts. In this way the degradation rate of the cross-linked terpolymer could be controlled. Regression analysis of sample mass loss％-degradation time showed that the degrading behavior were in accordance with pseudo first-order kinetics. As the ratio of NVP content going up, the pseudo first-order reaction rate constant k' increased, while the degradation half-life decreased. In the early stage of the degradation, the instant degradation rate went up with the increase of n(NVP); While in the late stage, the rate decreased with the increase of n(NVP). The study showed that the degradation of cross-linked PLA terpolymer was possible to be adjusted delicately. That was the development in this study compared with pure PLA which could be controlled only by molecular weight or crystallization degree.The cross-linked controllable biodegradable biomaterials obtained in this study have shown the remarkable improvement in terms of hydrophilicity, mechanical properties, controllable degrading rate and cellular biocompatibility.