טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentMakarov Carina
SubjectBioresorbable Calcium Phosphate Ceramic-Polymer
Nanocomposites for Load Bearing Bone Healing
Devices - Low Temperature Synthesis and
Drug Incorporation
DepartmentDepartment of Materials Science and Engineering
Supervisors Professor Elazar Gutmanas
Dr. Irena Gotman
Full Thesis textFull thesis text - English Version


Abstract

     In orthopedic research, increasing attention is being paid to bioresorbable composite materials as an attractive alternative to permanent metal bone healing devices. Typical composites consist of a biodegradable polyester matrix loaded with bioactive calcium phosphate ceramic particles (tricalcium phosphate, TCP or hydroxyapatite, HA) added to improve the biological response and mechanical properties of the neat polymer. The mechanical behavior of such particle-reinforced composites, however, falls far short of the expected performance in high-load bearing situations. Replicating some features of nacre - a strong and tough natural nanocomposite with a very high content of brittle inorganic phase, can pave the way for a new generation of high-strength resorbable bone implants. This research concentrated on the processing of such “bio-inspired” nanocomposites with high calcium phosphate content where the strong ceramic skeleton is toughened by a small amount of continuously dispersed polymer component. An original high pressure consolidation method was employed to fabricate dense bulk nanocomposites without exposing them to high processing temperatures. This allowed for incorporation of antibacterial drugs that can be released from the implanted device to prevent infection.

   Ca deficient HA and b-TCP-based nanocomposites toughened with 10 to 40 vol.% biodegradable polymer (PLA or PCL) were produced by in situ processing or solution mixing. High compressive strengths were achieved for practically all ceramic-polymer combinations. For b-TCP-PLA composites, a continuous polymer network was formed when PLA content exceeded 15 vol.%. Such composites exhibited a few percent ductility and high bending strengths (up to 75 MPa), especially when consolidated at slightly elevated temperatures to ?95 % density. These properties are significantly better than the data reported for more conventional biodegradable polymer-based composites reinforced with small volume fractions of CaP particles.

   Sustained drug release of incorporated antibiotic drug - vancomycin - spanning for over two weeks was measured for b-TCP-PLA composites high pressure consolidated at room temperature and 120°C. The drug retained enough of its antibacterial activity to cause a significant decrease in bacterial viability and to inhibit bacterial growth around the composite specimen. Finally, selected CaP-polymer nanocomposites were assessed in monocultures of endothelial cells (EC) and osteoblasts and in co-culture thereof and were shown to support the attachment and proliferation of these cell lines and the formation of pre-vascular structures by EC.

   The results of the research suggest that the developed CaP-PLA and CaP-PCL nanocomposites with high ceramic contents are promising candidate materials for resorbable load-bearing bone healing devices with drug delivery capability.