© 2022 Elsevier B.V.Silk produced by silkworms or spiders offers biocompatibility, biodegradability, stability, and biomechanical strength, making it an excellent biomaterial for wound bandages/dressings and skin grafts. Silk scaffolds are also bioactive matrices necessary to restore the healing cascade and barrier properties that induce skin organogenesis in chronic wounds. Silk-based composites are being used to protect wounds from infections. Many studies were conducted via 2D cell culture and in vivo approaches to explain the interaction between skin tissue and silk. In addition to the difficulties that 2D cell culture techniques have in mimicking skin tissue, the physiological differences and immunological incompatibility between in vivo models and human skin tissue make it more complicated to understand the effectiveness of silk scaffolds. This leads to excessive experimental animal usage and false positive or negative results for the clinical stage. Alternatively, organ-like microtissues (organoids, spheroids, among others) produced using stem cells can be a real stakeholder in measuring the success of wound patches due to their 3D structure, cellular diversity, and high yield. However, the fabrication procedure of the microtissues is highly Matrigel-dependent, and it is not the best choice for the studies due to its indeterminate nature, protein concentration, and composition. Silk-based nano-biocomposites can be a good candidate owing to their features above for 3D skin cell culture studies. Here, we evaluated the current applications of silk-based materials in wound healing and their possible applications in 3D tissue engineering for microtissues.