Urethral Microenvironment Adapted Sodium Alginate/Gelatin/Reduced Graphene Oxide Biomimetic Patch Improves Scarless Urethral Regeneration

The nasty urine microenvironment (UME) is an inherent obstacle that hinders urethral repair due to fibrosis and swelling of the oftentimes adopted hydrogel-based biomaterials. Here, using reduced graphene oxide (rGO) along with double-freeze-drying to strengthen a 3D-printed patch is reported to realize scarless urethral repair. The sodium alginate/gelatin/reduced graphene oxide (SA/Gel/rGO) biomaterial features tunable stiffness, degradation profile, and anti-fibrosis performance. Interestingly, the 3D-printed alginate-containing composite scaffold is able to respond to Ca2+ present in the urine, leading to enhanced structural stability and strength as well as inhibiting swelling. The investigations present that the swelling behaviors, mechanical properties, and anti-fibrosis efficacy of the SA/Gel/rGO patch can be modulated by varying the concentration of rGO. In particular, rGO in optimal concentration shows excellent cell viability, migration, and proliferation. In-depth mechanistic studies reveal that the activation of cell proliferation and angiogenesis-related proteins, along with inhibition of fibrosis-related gene expressions, play an important role in scarless repair by the 3D-printed SA/Gel/rGO patch via promoting urothelium growth, accelerating angiogenesis, and minimizing fibrosis in vivo. The proposed strategy has the potential of resolving the dilemma of necessary biomaterial stiffness and unwanted fibrosis in urethral repair. A sodium alginate/gelatin/rGO biomimetic patch is created with printable, degradable, and adjustable mechanical properties. The inclusion of rGO with the appropriate concentration can promote cell migration, and proliferation, and inhibit urethral fibrosis and the formation of the urothelium. This strategy demonstrates great potential in addressing the dilemma of necessary biomaterial stiffness and unwanted fibrosis in urethral repair.image