The objective of the present study was to evaluate non-woven collagen/poly(lactic-co-glycolic acid) fibrous scaffold (Col/PLGA FS) prepared by a co-electrospinning process using a novel multi syringe electrospinning system for dura repair. The morphological and mechanical properties of the fibrous scaffolds (FSs) were assessed by scanning electron microscopy (SEM) and a universal testing machine (UTM). The changes in chemical composition due to the incorporation of collagen into PLGA were determined by Fourier transform infrared spectroscopy-attenuated total reflection mode (FTIR-ATR). The biocompatibility of the FSs was also evaluated in vitro in cultures of mouse fibroblasts and in vivo by subcutaneous implantation studies in rats. SEM images of the samples showed that the fiber size distribution of Col/PLGA FS became narrow compared to that of PLGA FS due to the incorporation of collagen with small fiber diameter. The FTIR-ATR spectrum of Col/PLGA FS revealed the characteristic bands of collagen and PLGA, indicating the co-existence of two fibrous structures. The poor mechanical properties of collagen FS were improved by co-electrospinning with PLGA. In vitro L929 cell proliferation assay revealed that the cyto-compatibility of Col/PLGA FS was increased compared to that of PLGA FS. In addition, Col/PLGA FS showed increased hydrophilic properties sufficient to absorb the exudates at the interface with mild foreign body reactions. In animal studies using a traumatic brain injury (TBI) model, the incorporation of collagen induced increased macrophage chemotaxis, and the post-inflammatory reaction of these cells led to remarkable brain tissue regeneration.