The advent of tissue engineering has invigorated interest in novel tissue regeneration matrices. An ideal matrix that simulates the natural extra cellular matrix (ECM) should be nanoscale, with three dimensionally interconnected nanofibers which cannot be generated by current methods such as electrospinning. Furthermore, certain biocompatible materials like silicon cannot be electrospun. We present a novel MHz laser synthesis method that permits sub-100 nm scale structures on any material, including silicon, that mimic the natural ECM. Owing to its three dimensional interlinked nature, the nanofibrous substrate is shown to guide the osteoblasts and fibroblasts to grow not only planarly to the surface, as is true for conventional scaffolds, but also expand and grow upward vertically. This method of synthesis demonstrates promise for novel three dimensional (3D) scaffolds that can assist in tissue and bone regeneration and a myriad of other applications such as drug delivery and biosensing.