Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–brain barrier, the barrier that reduces cancer therapy efficacy. Here, we tested three alternative GQDs’ surface chemistries on two neural lineages (glioblastoma cells and mouse cortical neurons). We showed that surface chemistry modulates GQDs’ biocompatibility. When used in combination with the chemotherapeutic drug doxorubicin, GDQs exerted a synergistic effect on tumor cells, but not on neurons. This appears to be mediated by the modification of membrane permeability induced by the surface of GQDs. Our findings highlight that GQDs can be adopted as a suitable delivery and therapeutic strategy for the treatment of glioblastoma, by both directly destabilizing the cell membrane and indirectly increasing the efficacy of chemotherapeutic drugs.

Craniosynostosis (CS) is the second most prevalent inborn craniofacial malformation; it results from the premature fusion of cranial sutures and leads to dimorphisms of variable severity. CS is clinically heterogeneous, as it can be either a sporadic isolated defect, more frequently, or part of a syndromic phenotype with mendelian inheritance. The genetic basis of CS is also extremely heterogeneous, with nearly a hundred genes associated so far, mostly mutated in syndromic forms. Several genes can be categorised within partially overlapping pathways, including those causing defects of the primary cilium. The primary cilium is a cellular antenna serving as a signalling hub implicated in mechanotransduction, housing key molecular signals expressed on the ciliary membrane and in the cilioplasm. This mechanical property mediated by the primary cilium may also represent a cue to understand the pathophysiology of non-syndromic CS. In this review, we aimed to highlight the implication of the primary cilium components and active signalling in CS pathophysiology, dissecting their biological functions in craniofacial development and in suture biomechanics. Through an in-depth revision of the literature and computational annotation of disease-associated genes we categorised 18 ciliary genes involved in CS aetiology. Interestingly, a prevalent implication of midline sutures is observed in CS ciliopathies, possibly explained by the specific neural crest origin of the frontal bone.

Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in pediatric surgical skull reconstruction, i.e., biodegradable bone fixation systems, biomimetic scaffolds, drug delivery systems, and cell-based approaches.

The molecular layer that adsorbs on the biomaterial surface upon contacting body tissues and fluids, termed the conditioning layer (CL), influences cell behavior regulating scaffold integration and resilience in a patient-specific fashion. To predict and improve the clinical outcome of 3D-printed scaffolds, graphene coatings are employed in bone tissue engineering, due to the possibility to functionalize its chemical/physical properties. In this study, we investigated the composition and the influence of the CL on three different graphene oxide-based coatings of 3D-printed polycaprolactone (PCL) implants: graphene oxide (–GO), carboxylated GO (–GO–COOH) and reduced GO (–rGO). The effects of surface features and CL were evaluated in vitro using bone marrow-derived mesenchymal stromal cells (hBM-MSC). Our results showed that the CL formed on negatively charged PCL–GO–COOH and PCL–rGO scaffolds reduced cell adhesion, while simultaneously enhancing cell cluster formation and proliferation by a fivefold increase. The quantification of bone mineralized matrix highlighted that CL on both PCL–GO–COOH and PCL–rGO coatings sustained the osteogenic potential of these two types of GO. The analysis of CL components adsorbed on the scaffolds revealed that the PCL–GO–COOH and PCL–rGO coatings tend to entrap specific patterns of serum proteins (e.g. anti-adhesive and osteogenic modulators) and ions (carbonate and phosphate), suggesting a correlation between these enriched components and the observed biological outcomes of conditioned scaffolds. Lastly, PCL–rGO coatings maintained unique antibacterial properties after in vitro simulated CL formation, representing a suitable promising strategy to improve bone grafting capable of shaping CL formation while preserving the favorable osteoinductive properties of scaffolds.

Philadelphia-Negative Myeloproliferative neoplasms (MPNs) are a diverse group of blood cancers leading to excessive production of mature blood cells. These chronic diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), can significantly impact patient quality of life and are still incurable in the vast majority of the cases. This review examines the mechanobiology within a bone marrow niche, emphasizing the role of mechanical cues and the primary cilium in the pathophysiology of MPNs. It discusses the influence of extracellular matrix components, cell-cell and cell-matrix interactions, and mechanosensitive structures on hematopoietic stem cell (HSC) behavior and disease progression. Additionally, the potential implications of the primary cilium as a chemo- and mechanosensory organelle in bone marrow cells are explored, highlighting its involvement in signaling pathways crucial for hematopoietic regulation. This review proposes future research directions to better understand the dysregulated bone marrow niche in MPNs and to identify novel therapeutic targets.

Craniosynostosis are a heterogeneous group of genetic conditions characterized by the premature fusion of the skull bones. The most common forms of craniosynostosis are Crouzon, Apert and Pfeiffer syndromes. They differ from each other in various additional clinical manifestations, e.g., syndactyly is typical of Apert and rare in Pfeiffer syndrome. Their inheritance is autosomal dominant with incomplete penetrance and one of the main genes responsible for these syndromes is FGFR2, mapped on chromosome 10, encoding fibroblast growth factor receptor 2. We report an FGFR2 gene variant in a mother and daughter who present with different clinical features of Crouzon syndrome. The daughter is more severely affected than her mother, as also verified by a careful study of the face and oral cavity. The c.1032G>A transition in exon 8, already reported as a synonymous p.Ala344 = variant in Crouzon patients, also activates a new donor splice site leading to the loss of 51 nucleotides and the in-frame removal of 17 amino acids. We observed lower FGFR2 transcriptional and translational levels in the daughter compared to the mother and healthy controls. A preliminary functional assay and a molecular modeling added further details to explain the discordant phenotype of the two patients.