Nanostructured polymer scaffolds for tissue engineering and regenerative medicine

The structural features of tissue engineering scaffolds affect cell response and must be engineered to support cell adhesion, proliferation and differentiation. The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells interact with prior to forming a new tissue. In this review, bone tissue engineering is used as the primary example for the sake of brevity. We focus on nanofibrous scaffolds and the incorporation of other components including other nanofeatures into the scaffold structure. Since the ECM is comprised in large part of collagen fibers, between 50 and 500 nm in diameter, well-designed nanofibrous scaffolds mimic this structure. Our group has developed a novel thermally induced phase separation (TIPS) process in which a solution of biodegradable polymer is cast into a porous scaffold, resulting in a nanofibrous pore-wall structure. These nanoscale fibers have a diameter (50-500 nm) comparable to those collagen fibers found in the ECM. This process can then be combined with a porogen leaching technique, also developed by our group, to engineer an interconnected pore structure that promotes cell migration and tissue ingrowth in three dimensions. To improve upon efforts to incorporate a ceramic component into polymer scaffolds by mixing, our group has also developed a technique where apatite crystals are grown onto biodegradable polymer scaffolds by soaking them in simulated body fluid (SBF). By changing the polymer used, the concentration of ions in the SBF and by varying the treatment time, the size and distribution of these crystals are varied. Work is currently being done to improve the distribution of these crystals throughout three-dimensional scaffolds and to create nanoscale apatite deposits that better mimic those found in the ECM. In both nanofibrous and composite scaffolds, cell adhesion, proliferation and differentiation improved when compared to control scaffolds. Additionally, composite scaffolds showed a decrease in incidence of apoptosis when compared to polymer control in bone tissue engineering. Nanoparticles have been integrated into the nanostructured scaffolds to deliver biologically active molecules such as growth and differentiation factors to regulate cell behavior for optimal tissue regeneration.