Healing and angiogenic properties of collagen/chitosan scaffolds enriched with hyperstable FGF2-STAB® protein: in vitro, ex ovo and in vivo comprehensive evaluation

Wound healing is a process regulated by a complex interaction of multiple growth factors including fibroblast growth factor 2 (FGF2). Although FGF2 appears in several tissue engineered studies, its applications are limited due to its low stability both in vitro and in vivo. Here, this shortcoming is overcome by a unique nine-point mutant of the low molecular weight isoform FGF2 retaining full biological activity even after twenty days at 37 °C. Crosslinked freeze-dried 3D porous collagen/chitosan scaffolds enriched with this hyper stable recombinant human protein named FGF2-STAB® were tested for in vitro biocompatibility and cytotoxicity using murine 3T3-A31 fibroblasts, for angiogenic potential using an ex ovo chick chorioallantoic membrane assay and for wound healing in vivo with 3-month old white New Zealand rabbits. Metabolic activity assays indicated the positive effect of FGF2-STAB® already at very low concentrations (0.01 µg/mL). The angiogenic properties examined ex ovo showed enhanced vascularization of the tested scaffolds. Histological evaluation and gene expression analysis by RT-qPCR proved newly formed granulation tissue at the place of a previous skin defect without significant inflammation infiltration in vivo. This work highlights the safety and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB® protein. Moreover, these sponges could be used as scaffolds for growing cells for dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration

Combined Orofacial Aspergillosis and Mucormycosis: Fatal Complication of a Recurrent Paediatric Glioma—Case Report and Review of Literature

9noMucormycosis and aspergillosis are two opportunistic fungal infections, which can evolve into life-threatening complications. They generally affect patients with relevant risk factors such as immunocompromisation or long-term use of antibiotics or corticosteroids. Treatment usually combines medical and surgical approaches, often including extended necrosectomies, although the prognosis of generalized fungal infections is very poor. In this paper, we present the case of a 17-year-old girl affected by combined aspergillosis and mucormycosis, following treatment of a recurrent glioma. The patient was hospitalized for a suspected cellulitis of the right hemi-face, involving frontal maxillary area and the upper airways and was immediately put on intravenous antibiotic therapies; after performing nasal septum and maxillary biopsies, concomitant mucormycosis and aspergillosis were diagnosed and antimycotic therapy with liposomal B-amphotericin was administered. After evaluation by the oral surgeon and otolaryngologist, surgical cranio-facial necrosectomy was suggested, but refused by the parents of the patient. The girl died only few days later, due to a respiratory arrest. Awareness of this pathology with prompt diagnosis and early treatment may improve the outcome of these infections and reduce the mortality.reservedmixedChermetz, Maddalena; Gobbo, Margherita; Rupel, Katia; Ottaviani, Giulia; Tirelli, Giancarlo; Bussani, Rossana; Luzzati, Roberto; Di Lenarda, Roberto; Biasotto, MatteoChermetz, Maddalena; Gobbo, Margherita; Rupel, Katia; Ottaviani, Giulia; Tirelli, GIAN CARLO; Bussani, Rossana; Luzzati, Roberto; DI LENARDA, Roberto; Biasotto, Matte