Smart thermosensitive polymer such as poly(N-isopropyl acrylamide) (PNIPAM) and dominant fibrous protein of connective tissue such as collagen (CLG) possess great potential in biomedical and tissue engineering applications. The objectives of current work aim to explore potential of PNIPAM and collagen by (i) establish a stable procedure to extract collagen from fresh water Tilapia fish scale (TFS) and (ii) fabricate PNIPAM and hybrid PNIPAM-CLG nanofibrous scaffolds through electrospinning technique and investigate their material-process-structure behaviour. Type I collagen was derived through acid hydrolysis of TFS. Electrospinning of PNIPAM was carried out with 16, 18 and 20 wt% PNIPAM concentration in methanol (MeOH) while PNIPAM-CLG was prepared through blending measured quantity of PNIPAM dissolved in water with collagen dissolved in acetic acid. Material properties, viscosity, morphology and thermo-physical behaviors of the derived collagen, electrospun PNIPAM and PNIPAM-CLG scaffolds were characterized. Results from SDS-PAGE and FTIR confirmed that the isolated TFS collagen is of type I. EDX revealed that demineralization eliminated the aluminium, magnesium, silicon and phosphorus while significantly reduced the sulfur elements from raw TFS. SEM observation of the collagen morphology shown a fluffy and fibrillary lamellae structure. Electrospun scaffolds were successfully fabricated with 16 and 18 wt% PNIPAM in MeOH. Both homogeneity and average fibre diameter (Davg) were greater in the 18 wt% PNIPAM scaffold, in which the Davg for 16 and 18 wt% were ∼110 and ∼131.7 nm respectively. However, PNIPAM at 20 wt% failed to be electrospun owing to its excessively high viscosity. On the other hand, SEM observation revealed that the electrospun hybrid PNIPAM-CLG scaffold has Davg of ∼105.5 nm amid the presence of numerous elongated beads.