Plasma-assisted multiscale topographic scaffolds for soft and hard tissue regeneration.

The design of transplantable scaffolds for tissue regeneration requires gaining precise control of topographical properties. Here, we propose a methodology to fabricate hierarchical multiscale scaffolds with controlled hydrophilic and hydrophobic properties by employing capillary force lithography in combination with plasma modification. Using our method, we fabricated biodegradable biomaterial (i.e., polycaprolactone (PCL))-based nitrogen gas (N-FN) and oxygen gas plasma-assisted flexible multiscale nanotopographic (O-FMN) patches with natural extracellular matrix-like hierarchical structures along with flexible and controlled hydrophilic properties. In response to multiscale nanotopographic and chemically modified surface cues, the proliferation and osteogenic mineralization of cells were significantly promoted. Furthermore, the O-FMN patch enhanced regeneration of the mineralized fibrocartilage tissue of the tendon-bone interface and the calvarial bone tissue in vivo in rat models. Overall, the PCL-based O-FMN patches could accelerate soft- and hard-tissue regeneration. Thus, our proposed methodology was confirmed as an efficient approach for the design and manipulation of scaffolds having a multiscale topography with controlled hydrophilic property.