Kim Sang-Soo, Sun Park Min, Jeon Oju, Yong Choi Cha, Kim Byung-Soo
Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
Biomaterials. 2006 Mar;27(8):1399-409. doi: 10.1016/j.biomaterials.2005.08.016. Epub 2005 Oct 5.
Biodegradable polymer/bioceramic composite scaffolds can overcome the limitations of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. However, conventional methods for fabricating polymer/bioceramic composite scaffolds often use organic solvents (e.g., the solvent casting and particulate leaching (SC/PL) method), which might be harmful to cells or tissues. Furthermore, the polymer solutions may coat the ceramics and hinder their exposure to the scaffold surface, which may decrease the likelihood that the seeded osteogenic cells will make contact with the bioactive ceramics. In this study, a novel method for fabricating a polymer/nano-bioceramic composite scaffold with high exposure of the bioceramics to the scaffold surface was developed for efficient bone tissue engineering. Poly(D,L-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/HA) composite scaffolds were fabricated by the gas forming and particulate leaching (GF/PL) method without the use of organic solvents. The GF/PL method exposed HA nanoparticles at the scaffold surface significantly more than the conventional SC/PL method does. The GF/PL scaffolds showed interconnected porous structures without a skin layer and exhibited superior enhanced mechanical properties to those of scaffolds fabricated by the SC/PL method. Both types of scaffolds were seeded with rat calvarial osteoblasts and cultured in vitro or were subcutaneously implanted into athymic mice for eight weeks. The GF/PL scaffolds exhibited significantly higher cell growth, alkaline phosphatase activity, and mineralization compared to the SC/PL scaffolds in vitro. Histological analyses and calcium content quantification of the regenerated tissues five and eight weeks after implantation showed that bone formation was more extensive on the GF/PL scaffolds than on the SC/PL scaffolds. Compared to the SC/PL scaffolds, the enhanced bone formation on the GF/PL scaffolds may have resulted from the higher exposure of HA nanoparticles at the scaffold surface, which allowed for direct contact with the transplanted cells and stimulated the cell proliferation and osteogenic differentiation. These results show that the biodegradable polymer/bioceramic composite scaffolds fabricated by the novel GF/PL method enhance bone regeneration compared with those fabricated by the conventional SC/PL method.
可生物降解的聚合物/生物陶瓷复合支架能够克服传统陶瓷骨替代物的局限性，如脆性和成型困难。然而，用于制造聚合物/生物陶瓷复合支架的传统方法通常使用有机溶剂（例如，溶剂浇铸和颗粒沥滤（SC/PL）法），这可能对细胞或组织有害。此外，聚合物溶液可能会覆盖陶瓷并阻碍其暴露于支架表面，这可能会降低接种的成骨细胞与生物活性陶瓷接触的可能性。在本研究中，开发了一种用于制造聚合物/纳米生物陶瓷复合支架的新方法，该方法可使生物陶瓷在支架表面高度暴露，以用于高效的骨组织工程。聚（D，L-乳酸-共-乙醇酸）/纳米羟基磷灰石（PLGA/HA）复合支架通过气体成型和颗粒沥滤（GF/PL）法制造，无需使用有机溶剂。与传统的SC/PL法相比，GF/PL法使HA纳米颗粒在支架表面的暴露显著更多。GF/PL支架呈现出相互连接的多孔结构，没有皮层，并且与通过SC/PL法制造的支架相比，具有优异的增强机械性能。两种类型的支架都接种了大鼠颅骨成骨细胞，并在体外培养或皮下植入无胸腺小鼠体内八周。与SC/PL支架相比，GF/PL支架在体外表现出显著更高的细胞生长、碱性磷酸酶活性和矿化。植入后五周和八周对再生组织的组织学分析和钙含量定量显示，GF/PL支架上的骨形成比SC/PL支架上更广泛。与SC/PL支架相比，GF/PL支架上增强的骨形成可能是由于HA纳米颗粒在支架表面的更高暴露，这使得能够与移植细胞直接接触并刺激细胞增殖和成骨分化。这些结果表明，与通过传统SC/PL法制造的支架相比，通过新型GF/PL法制造的可生物降解聚合物/生物陶瓷复合支架增强了骨再生。
