Transforming Nanofiber Mats into Hierarchical Scaffolds with Graded Changes in Porosity and/or Nanofiber Alignment

A method for generating hierarchical scaffolds with graded changes in porosity and/or fiber alignment through solution-masked, vapor-induced welding of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers is reported. The success of this method relies on the fact that the PLGA nanofibers are swollen and welded more slowly by ethanol when immersed in its aqueous solution relative to direct exposure to its vapor. For a mat composed of random nanofibers, the treatment generates a gradation in porosity (both surface and bulk), with the over-welded region evolving from a highly porous mat into a dense film. If uniaxially aligned nanofibers are involved, however, graded changes are observed in both surface porosity and fiber alignment. When bone marrow stem cells are cultured on such a scaffold, they exhibit highly organized and random morphologies on the regions of uniaxially aligned nanofibers and dense film, respectively, with gradual changes in between. Such a scaffold shows promise in mimicking the connective tissue, such as the tendon-to-bone insertion, that relies on a graded transition in cell morphology from uniaxially aligned to random.