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ABSTRACT: Advanced frontal sinus disease non-responsive to conservative therapy has been treated with fat obliteration for decades. More recently, a wide variety of autogenous, allogenic or synthetic materials have also been used. In this study we present a treatment based on totally autogenous procedures and materials that was successfully implemented in 10 patients and followed up for a period of 6-10 years, to evaluate the feasibility of a new approach for the treatment of frontal sinus disease and other related cranial osseous derangements, based on regenerative medicine as an alternative to fat or other obliterating or grafting materials. Platelet-rich and -poor plasma (PRP, PPP) are set to clot with cortical shavings from the skull surface. After surgically stimulating the sinus to encourage cell chemotaxis, migration and homing, the bioactive scaffold is placed and covered with a PPP membrane and a periosteal flap. Ten patients with pathologies ranging from devastating infection to invasive tumours or trauma were treated with this regenerative procedure in a single-stage surgery. All patients had an uneventful recovery with bone formation and no complications or recurrences over the years. The application of modern principles in tissue regeneration and wound healing has resulted in a favourable outcome, with no complications or sequelae, in a series of 10 patients with advanced frontal sinus disease over a long period of time. Copyright © 2012 John Wiley & Sons, Ltd.