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徐洋(吉林大学,2007-2010,博士)
Title: Novel op-HA /PLGA composites: Preparations and experimental study on the
Osteogenic activity
Author: Xu Yang
Speciality: plastic surgery


Abstract:

Bone defect caused by Congenital defects, trauma or tumor is a common problem in clinicsal treatment. The state of the art in repairing, such as autologous or allogeneic bone transplantation, has a lot of drawbacks in varying degrees, respectively. For example,although autologous bone substitution is the best option, but the amount of autologous bone is extremely limited and the infect at donor sites, limited shape, size and amount of graft are the major drawbacks of this methods. While the allogeneic bone was used, although the size and amount of allogeneic bone could satisfy the requirement of bone transplant, its applications are limited sharply due to the suffering venture of inevitable immune response and virus disease transmission. Bone Tissue engineering aims at the repairing and restoring damaged or diseased tissue .function employing three fundamental “tools”, namely biological scaffolds, cells, and bioactive molecules. Scaffolds are central components of tissue engineering because they provide a three-dimensional structure for in vitro or in vivo cells ingrowth and inducing tissue and organ regeneration [2] . They usually act as a temporary substitute for the extracellular matrix and must have both appropriate structural and functional properties.HA/PLGA has been widely applied in plastic and oral surgery ,The composition of HA and PLGA could improve the mechanical strength and osteogenic activity of PLGA. But organic macromolacule and inorganic nano-particles of the composite are blended physically, the poor interfacial binding strength of organic and inorganic components results in low strength property unsuited for bone fixation and repair. In order to overcome this disadvantages, the novel composite of modified nano-HA was prepared. Nano-HA surface was grafted by LAc oligomer to prepare modified HA (op-HA). LAc oligomer on p-HA surface could extend into PLGA and enhance the interface adhesion between the two phases (op-HA and PLGA). So the mechanical strength of the material was increased. The mechanical strengths and chemical property, biocompatibility and the ability of bone forming were performed by instrument analysis, cell culture, animal experiments detection. The comprehensive property of ungrafted HA and the composites with different graft ratio of op-HA were analyzed. The optimal graft ratio of op-HA/PLGA would be obtained. It could provide bases for the medical application and industrialization of the novel material.
In the present study, the freeze-drying technique of 1,4-dioxane as a solvent was explored to fabricate porous nanocomposite scaffolds of PLGA and HA nanoparticles surface grafted with LAc oligomer (op-HA). The scaffolds with pore arrangement and highly
interconnected macro/microporous structure were prepared with different freezing dry conditions. The pore microstructure, the surface topography, and the mechanical properties, as well as the cell penetration and cell viability of these scaffolds were investigated, and the optimal production condition was assessed. It provides a basis for clinical applications.
conclusion: The novel type of scaffolds can be used in bone repair, op-HA/PLGA, possesses good biocompatibility, perfect cell adhesion and proliferation properties. modification of the op-HA composites improved bonding strength between two phases, reinforcing material dispersion and stability. When graft ratio Lactic acid oligomer to the surface of n-HA is high, the material mechanical properties, biocompatibility and osteogenic bioactivity and bone repair effects are bad.The new bone repair scaffolds 1% op-HA/PLGA composite bone repair material has a better cell adhesion, proliferation and osteogenic activity, Porous nanocomposite scaffolds of op-HA/PLGA with a honeycomb monolith structure were prepared by the one phase solution freeze-drying method in this study. The freezing temperature played a critical role in formation of the highly porous structure with a high
degree of interconnection. The average pore diameter varied from 167.2 ± 62.6 μm to 11.9 ± 4.2 μm as the freezing temperatures were changed from 4°C to -196°C. The 4°C freezing temperature scaffold showed better cell penetration and increased cell proliferation because of its larger pore size, higher porosity and interconnection. Although its compressive mechanical property was lower than the others, it will be acceptable for replacement of nonbearing bone.

The further study will focus on the preparation of scaffolds with both highly porous structures and high mechanical properties by adjusting the production conditions including solution concentration, freezing temperature and freezing rate.


Key words:
Nano-hydroxyapatite, Poly (lactide-co-glycolide), Composite, Tissue engineering scaffold, Biocompatibility, mineralization, Bone repair, Freeze-drying, Honeycomb monolith structure