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The development of highly porous cell supportive polymeric scaffolds with sufficient mechanical strength has always been a challenging task in tissue engineering. The widely used nanofiber fabrication methods like electrospinning are time consuming and the obtained nanofibrous scaffolds are generally consist of compactly packed fibers, which affect proper cell penetration. On the other hand, air-jet spinning is an upcoming, less explored alternative approach for generating loosely arranged nanofibrous scaffolds within short time. However, air-jet spun scaffolds show inferior mechanical properties due to loosely organized fibers. Herein, we report the fabrication and detailed characterization of polycaprolactone (PCL) tissue engineering scaffolds loaded with diamond nanosheets (DNS) by air-jet spinning. Our results showed that the inclusion of DNS could improve the mechanical strength of the scaffolds. In vitro biocompatibility, and in vivo implantation studies demonstrated that PCL-DNS scaffolds are highly biocompatible and are suitable for tissue engineering applications. Our studies showed that mammalian cells can proliferate well in the presence of PCL-DNS scaffolds and the nanocomposite scaffolds implanted in rats did not show any considerable adverse effects. Overall, the findings show that the developed novel air-jet spun PCL-DNS nanocomposite scaffolds can be used as cell supportive scaffolds for various tissue engineering applications. [Display omitted] • Diamond nanosheets loaded Air-jet spun PCL scaffolds were fabricated. • Diamond nanosheets improved the mechanical properties of PCL scaffolds. • Diamond nanosheets loaded scaffolds were biocompatible in vitro and in vivo. [ABSTRACT FROM AUTHOR]