Effects of fragmented polycaprolactone electrospun nanofiber in a hyaluronic acid hydrogel on fibroblasts

Hyaluronic acid (HA) hydrogels have shown promise as biomaterials for soft tissue engineering applications due to their biocompatibility and ability to mimic the extracellular matrix (ECM). However, their limited cell adhesion properties and the need for improved crosslinking methods have hindered their widespread use. In this study, we developed an ECM-mimicking HA hydrogel reinforced with alkaline hydrolyzed (1 M NaOH) fragmented (1.5 cm×1.5 cm) electrospun polycaprolactone (PCL) fibers to enhance cell adhesion and mechanical properties of HA hydrogel. Formation of HA hydrogel was achieved through a thiol-ene click reaction, which is initiated by exposure to visible blue light-activated biocompatible photoinitiator, riboflavin phosphate. The incorporation of alkaline hydrolyzed PCL fiber fragments (PFF) (0 %, 0.1 %, and 1 % w/v) into HA hydrogel precursor solution significantly increased the mechanical stiffness of the HA hydrogel, with the storage modulus ranging from 18.6 ± 0.7 Pa to 216.0 ± 38.2 Pa. The cytocompatibility of the PCL fiber-reinforced HA hydrogel was evaluated using NIH/3T3 fibroblasts. The results demonstrated improved cell adhesion, proliferation, and enhanced cellular functions, including increased production of glycosaminoglycans (GAGs) and collagen, in the PCL fiber-reinforced HA hydrogel compared to the control HA hydrogel. These findings suggest that the developed PCL fiber-reinforced HA hydrogel system, with tunable mechanical properties and excellent cytocompatibility, has potential applications in soft tissue engineering and regenerative medicine.