In the last decades a variety of innovative craniofacial approaches has been adopted to entire skull base. The endonasal endoscopic route has emerged as a suitable methodology for several skull base lesions. An effective watertight closure is essential to isolate the intracranial cavity in order to restore the natural intra and extradural compartment division, necessary to prevent postoperative cerebrospinal fluid (CSF) leakage and complications such as meningitis, brain herniation, and tension pneumocephalus. The reconstruction can be performed using different materials, both autologous (autologous grafts) and non-autologous, individually or combined in a multilayer fashion. The harvesting a nasoseptal flap is one of the most effective techniques: it reinforces the skull base closure granting isolation of the surgical field. The current study was focused on the development of new advanced devices and techniques, aiding in reducing postoperative CSF leak, which is one of the most feared complication of this surgical procedure. Additive manufacturing allows to design devices with tailored structural and functional features, in order to satisfy all the requirements. On the other hand, the development of injectable semi-IPNs and composites clearly benefits from specific mechanical/rheological and injectability studies. Accordingly, starting from some basic concepts, innovative principles and strategies were also proposed towards the design of additively manufactured and injectable devices.