| Biodegradable PLGAs have been widely investigated for use as tissue engineering devices, however, limitations include: insufficient porosity, low mechanical strength, immunogenicity, heterogeneous degradation, and low cell affinity. This research investigated the potential advantages of fabricating scaffolds by blending PLGA with PEG to deliver rhBMP-2 for bone regeneration applications.; The manufacturing process was found to be the most significant factor influencing the thermo-mechanical properties of the scaffolds regardless of the concentration and molecular weight of PEG used. Blended PLGA:PEG scaffolds fabricated using compression, heat-molding, and high molecular weight PEGs (10 and 20 kDa) had sufficient mechanical strength for bone scaffolding applications as shown by a compressive modulus comparable to trabecular bone. Thermal properties of the scaffolds showed that amorphous solid-state miscibility was not responsible for changes in mechanical strength, however changes in melting temperatures was dependent on fabrication method. We demonstrated the ability to use blending and fabrication processes to design biodegradable scaffolds for a range of biomedical applications.; Combinations of initial processes were used to design strong and uniform devices that demonstrated minimal in vitro immune response. With high moduli and plastic deformation the modified, compressed scaffolds showed significant promise for use as bone regenerating devices. The adhesion of macrophages to PLGA scaffolds was dependent upon method of fabrication as well as blending with PEG. The presence of PEG in the polymeric scaffolds reduced macrophage attachment in all blends compared to PLGA controls. We established that the modified compression method produced scaffolds demonstrating mechanical strength similar to bone as well as reduced macrophage attachment.; To further characterize the modified compression method, in vitro degradation as well as preosteoblast attachment and differentiation in the presence of rhBMP-2-containing scaffolds was studied. The degradation rate of PLGA scaffolds was slowed significantly during weeks 1 and 2 by blending PLGA with PEG, attributable to reduced acid-catalyzed degradation. Upon incubation with preosteoblasts, the PLGA:BMP formulation was the only scaffold to demonstrate increased ALP activity. We showed that PEG and rhBMP-2 inclusion in PLGA scaffolds was able to alter degradation rate, thermo-mechanical properties, preosteoblast attachment, and preosteoblast ALP production. |
