An In Vitro Macrophage Response Study of Silk Fibroin and Silk Fibroin/Nano-Hydroxyapatite\nScaffolds for Tissue Regeneration Application

In recent years, silk fibroin (SF) has been incorporated\nwith low\ncrystallinity nanohydroxyapatite (nHA) as a scaffold for various tissue\nregeneration applications due to the mechanical strength of SF and\nosteoconductive properties of nHA. However, currently, there is a\nlack of understanding of the immune response toward the degradation\nproducts of SF with nHA composite after implantation. It is known\nthat particulate fragments from the degradation of a biomaterial can\ntrigger an immune response. As the scaffold is made of degradable\nmaterials, the degradation products may contribute to the inflammation.\nTherefore, in this study, the effects of the enzymatic degradation\nof the SF/nHA scaffold on macrophage response were investigated in\ncomparison to the control SF scaffold. Since the degradation products\nof a scaffold can influence macrophage polarization, it can be hypothesized\nthat as the SF and SF/nHA scaffolds were degraded in vitro using protease\nXIV solution, the degradation products can contribute to the polarization\nof THP-1-derived macrophages from pro-inflammatory M1 to anti-inflammatory\nM2 phenotype. The results demonstrated that the initial (day 1) degradation\nproducts of the SF/nHA scaffold elicited a pro-inflammatory response,\nwhile the latter (day 24) degradation products of the SF/nHA scaffold\nelicited an anti-inflammatory response. Moreover, the degradation\nproducts from the SF scaffold elicited a higher anti-inflammatory\nresponse due to the faster degradation of the SF scaffold and a higher\namino acid concentration in the degradation solution. Hence, this\npaper can help elucidate the contributory effects of the degradation\nproducts of SF and SF/nHA scaffolds on macrophage response and provide\ngreater insights into designing silk-based biomaterials with tunable\ndegradation rates that can modulate macrophage response for future\ntissue regeneration applications.