Unraveling the role of shell hydrophilicity of core-shell microspheres on fibroblast cell bioactivity as biostimulators.

Core-shell microspheres have shown great potential in the field of biomedical applications, especially in drug delivery, tissue repair, and regenerative medicines, due to their dual properties and multifunctionality. Although the benefits of core-shell microspheres have been advocated in many applications, the role of core-shell microspheres composed of materials of different natures as implants has not been revealed, especially in the interaction between hydrophobic polycaprolactone and hydrophilic alginate materials with fibroblasts cells. This study successfully prepared core-shell microsphere structures of PCL@Alg with hydrophobic outer shell wrapped on a hydrophilic inner core and Alg@PCL with hydrophilic outer shell wrapped on a hydrophobic inner core structure. PCL@Alg The microspheres treated group showed highest cell viability (172.85 %), and highest wound closure rate, reaching 58.34 %. The hydrophilic outer layer of Alg@PCL promoted aligned cell growth around the shell where a dense layer of cells was found surrounding the hydrophilic alginate shell after 24 h incubation. The ELISA results suggested that PCL@Alg microspheres significantly promoted COX-2 production (233.32 pg/mL), while IL-6 levels were the lowest among all treatment groups (17.36 pg/mL). In addition, PCL@Alg microspheres have a significant promoting effect on the synthesis of COL-III (92.25 ng/mL) and COL-I (32.85 ng/mL) as compared to porous PCL microsphere (PMN). The core-shell microsphere wiith hydrophobic PCL shell benefit the production of collagen at accelerated cell growth and migration rate while the inflammation level was remained low. These findings could inspire design application of core-shell microsphere with particular shell thickness for future consideration, paving the way for core-shell microspheres as regenerative treatments for dermal fibroblasts in a safer manner.