Nanoscale agents within 3D-printed constructs: intersection of nanotechnology and personalized bone tissue engineering

Tissue engineering offers a solution to the worldwide shortage of bone substitutes for clinical implantation. Although the technique has been greatly improved since its first inception, one of the current problems it encounters is the lack of functionality, i.e., production of fully functional tissues and organs. This functionality could be achieved through the induction and control of cellular behavior within the tissue-engineered constructs to provide differentiation, mineralization, and vascularization. It is well documented that cellular activities in the body are strictly controlled and regulated by growth factors of several types. Therefore, controlled delivery strategies to mimic the bioavailability of the bioactive agents including growth factors became an important strategy in functional tissue engineering approaches. Moreover, the architecture of the scaffolds has absolute importance along with adaptability to the defect site so that cell behavior can be managed since the driving force of cellular activities and interconversions of the connective tissue cells (osteoblasts, chondrocytes, and fibroblasts) depend on their geometry and adhesion characteristics. 3D printing offers an important advancement along with this aim, which unites computer-aided design and computer-aided manufacturing approaches to obtain personalized structures. In this review, recent advancements in the incorporation of nanoscale agents to prepare nanocomposites as well as to produce controlled delivery platforms by using nanoparticles are described by special emphasis on 3D-printed bone tissue engineering applications.