Title: A novel biodegradable polymeric nano-composite for bone repair:
preparation and experimental study on the repairing of bone defect
Ph D: Cui Yang
Speciality: surgery
Abstract:
Bone defect and nonunion induced by trauma or tumor are still the puzzles of
reconstructive orthopaedic surgery nowadays. Although autologous and allogeneic
bone substitute materials, as the common replaceable materials, play important
role in treatments, they still have many intrinsic disadvantages and can not meet
the demands in all situations. Autologous bone grafts are considered to be the
optimal selection,but the morbidity at donor sites,limited shape,size and amount of
graft are the major drawbacks of this technique. Furthermore,the additional
surgery makes patient undergo more injuries to body, including pain and infection.
Allogeneic bone material can be prepared into any shape,size needed in surgery
without the limits of amount,however the inevitable immune response and the risk
of virus disease transmission make it limit to application. In order to overcome the
limitation of the two methods, it is important task to develop the better man-made
biological material to repair bone defect.
The biodegradable material of hadroxyapatite and polylactide(HA/PLA)
owns good biocompatibility and osteoconductivity. Because of similar constitutes
to bone matrix, the composite possesses great bone-bonding properties. It is a kind
of promising material for bone fixation and repair. However, organic
macromolacule and inorganic nano-particles of the composite are blended
physically, the poor interface adhesion of two phases (p-HA and PLGA) results in
ill strength property unsuited for bone fixation and repair. What’s more, the
degradation period of material is unequal to bone growth speed.
In order to overcome the disadvantages, the novel composite of modified
nano-HA and PLGA was prepared. Nano-HA surface was grafted by LAc
oligomer to prepare modified HA (p-HA), then blended with PLGA to get the
composite p-HA/PLGA. Modified p-HA particles owned good uniform dispersion
in PLGA. LAc oligomer on p-HA surface could extend into PLGA and enhance
the interface adhesion between the two phases. The mechanical strength of the
material was increased. The degradation period could be adjusted by the various
ratios of LA and GA in PLGA. The osteoconductivity of p-HA and degradable
property of PLGA were combined, and the biocompatibility was enhanced. The
novel composite was suitable for the requirement of clinical bone repair.
As a novel material, biocompatibilty would be the most important index to be
considered. And then the mechanical property and osteogenic activity should also
be thought about. The composites with different ratio of p-HA to PLGA were
prepared. Then the three-dimensional scaffolds of bone tissue engineering with
certain pores and porosity were prepared by melt-molding/particle leaching
method.
The comprehensive evaluation of physicochemical property, mechanical
strength, biocompatibility and the osteogenic ability were performed by
instrument analysis, cell culture, animal experiments and molecular biological
detection. The comprehensive property of ungrafted HA, grafted HA and the
composites with various contents of p-HA were analyzed. The optimal blend ratio
of two phases of p-HA/PLGA would be obtained. It could provide bases for the
medical application and industrialization of the novel material.
Conclusion: The new bone repair material of p-HA/PLGA shows
satisfactory biocompatibility and good ability of cell adherence and proliferation.
Modified p-HA could enhance the interface adhesion between two phases, and the
dispersive capacity as well as the stable ability could also be enhanced. The
mechanical strength and bone repair ability are not satisfied if p-HA account more
or less than the suitable ratio. The mRNA expressions of Collagen-I and
Collagen-II are higher for PLGA and 5%p-HA/PLGA, BMP-2 mRNA expressions
are higher for 20%p-HA/PLGA and HA/PLGA, OCN mRNA expressions are
higher for HA/PLGA and PLGA. The 20% p-HA/PLGA shows good
comprehensive property.
Key Words: modified hydroxyapatite, PLGA, nano-composite, scaffold for
tissue engineering, biocompatibility, bone repair