Study of the effects of different biomaterials on osteogenic differentiation of oral-periosteal cells

Bone regeneration is currently one of the most important challenges for regenerative medicine and it is considered an ideal clinical strategy in the maxillo-facial area [1]. Bone resorption of alveolar crest occurring after tooth extraction leads to several risks for future treatments, including dental implants. For this reason, alveolar ridge preservation (ARP) has become a key component of contemporary clinical dentistry. Several clinical techniques and bone substitute materials can be used to fill the socket after tooth extraction. For all of them, the principle aim is to keep the shape and the size of the bone socket of the extracted tooth allowing inserting the dental implants [2]. The goal of our study was to compare different biocompatible scaffolds based on PLGA (Fisiograft®), Bioglass (Activioss®) and collagen (Sombrero®) in an in vitro model of tissue engineering for dental applications. The cells used in our study derived from Periosteum obtained from four different patients that underwent socket preservation selected by the School of Dentistry of the University of Pavia, previous informed consent. We created bio-complexes constituted by mesenchymal-periosteal cells seeded on different types of biomaterials and we performed adhesion, morphological, proliferative and bone differentiation analyses at different time points (7, 14 and 28 days of culture) in proliferative and osteogenic conditions. Bone differentiation was evaluated by qRT-PCR on genes involved in osteoblast development, like BMP-2, Osteocalcin and Periostin. Our results demonstrated that Sombrero® enhanced adhesion and proliferation of periosteal cells, as highlighted by Haematoxylin-Eosin staining and XTT test (3 and 7 days). Long-term studies (14 and 28 days) demonstrated that periosteal differentiation is about the same among the different materials tested. From these preliminary studies we can conclude that it could be advantageous the clinical use of both collagenic and PLGA scaffolds in order to ameliorate initial colonization and subsequent mechanical support in maxillo-bone regeneration. This work was supported by grant from NATO 2016 (“RAWINTS” (G-984961): RApid Skin Wound healing by INtegrated Tissue engineering and Sensing)

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery

Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too

Evaluation of Poly(Lactic-co-glycolic) Acid Alone or in Combination with Hydroxyapatite on Human-Periosteal Cells Bone Differentiation and in Sinus Lift Treatment

Most recent advances in tissue engineering in the fields of oral surgery and dentistry have aimed to restore hard and soft tissues. Further improvement of these therapies may involve more biological approaches and the use of dental tissue stem cells in combination with inorganic/organic scaffolds. In this study, we analyzed the osteoconductivity of two different inorganic scaffolds based on poly (lactic-co-glycolic) acid alone (PLGA-Fisiograft) or in combination with hydroxyapatite (PLGA/HA-Alos) in comparison with an organic material based on equine collagen (PARASORB Sombrero) both in vitro and in vivo. We developed a simple in vitro model in which periosteum-derived stem cells were grown in contact with chips of these scaffolds to mimic bone mineralization. The viability of cells and material osteoconductivity were evaluated by osteogenic gene expression and histological analyses at different time points. In addition, the capacity of scaffolds to improve bone healing in sinus lift was examined. Our results demonstrated that the osteoconductivity of PLGA/HA-Alos and the efficacy of scaffolds in promoting bone healing in the sinus lift were increased. Thus, new clinical approaches in sinus lift follow-up should be considered to elucidate the clinical potential of these two PLGA-based materials in dentistry

Evaluation of Poly(Lactic-co-glycolic) Acid Alone or in Combination with Hydroxyapatite on Human-Periosteal Cells Bone Differentiation and in Sinus Lift Treatment

Most recent advances in tissue engineering in the fields of oral surgery and dentistry have aimed to restore hard and soft tissues. Further improvement of these therapies may involve more biological approaches and the use of dental tissue stem cells in combination with inorganic/organic scaffolds. In this study, we analyzed the osteoconductivity of two different inorganic scaffolds based on poly (lactic-co-glycolic) acid alone (PLGA-Fisiograft) or in combination with hydroxyapatite (PLGA/HA-Alos) in comparison with an organic material based on equine collagen (PARASORB Sombrero) both in vitro and in vivo. We developed a simple in vitro model in which periosteum-derived stem cells were grown in contact with chips of these scaffolds to mimic bone mineralization. The viability of cells and material osteoconductivity were evaluated by osteogenic gene expression and histological analyses at different time points. In addition, the capacity of scaffolds to improve bone healing in sinus lift was examined. Our results demonstrated that the osteoconductivity of PLGA/HA-Alos and the efficacy of scaffolds in promoting bone healing in the sinus lift were increased. Thus, new clinical approaches in sinus lift follow-up should be considered to elucidate the clinical potential of these two PLGA-based materials in dentistry

Circulating microRNAs and Their Role in Multiple Myeloma

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow infiltration of clonal plasma cells. The recent literature has clearly demonstrated clonal heterogeneity in terms of both the genomic and transcriptomic signature of the tumor. Of note, novel studies have also highlighted the importance of the functional cross-talk between the tumor clone and the surrounding bone marrow milieu, as a relevant player of MM pathogenesis. These findings have certainly enhanced our understanding of the underlying mechanisms supporting MM pathogenesis and disease progression. Within the specific field of small non-coding RNA-research, recent studies have provided evidence for considering microRNAs as a crucial regulator of MM biology and, in this context, circulating microRNAs have been shown to potentially contribute to prognostic stratification of MM patients. The present review will summarize the most recent studies within the specific topic of microRNAs and circulating microRNAs in MM

Circulating microRNAs and their role in multiple myeloma

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow infiltration of clonal plasma cells. The recent literature has clearly demonstrated clonal heterogeneity in terms of both the genomic and transcriptomic signature of the tumor. Of note, novel studies have also highlighted the importance of the functional cross-talk between the tumor clone and the surrounding bone marrow milieu, as a relevant player of MM pathogenesis. These findings have certainly enhanced our understanding of the underlying mechanisms supporting MM pathogenesis and disease progression. Within the specific field of small non-coding RNA-research, recent studies have provided evidence for considering microRNAs as a crucial regulator of MM biology and, in this context, circulating microRNAs have been shown to potentially contribute to prognostic stratification of MM patients. The present review will summarize the most recent studies within the specific topic of microRNAs and circulating microRNAs in MM

Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited anti-tumor activity

34siThe multiple myeloma (MM) mutational landscape has identified alterations in KRAS as the most recurring somatic variant. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying that KRASG12C mutation. Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We have used AZD4785, a potent and selective antisense oligonucleotide (ASO) which selectively targets and down-regulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche; and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, confirming KRAS as a driver and a therapeutic target in MM.reservedmixedSacco, Antonio; Federico, Cinzia; Todoerti, Katia; Ziccheddu, Bachisio; Palermo, Valentina; Giacomini, Arianna; Ravelli, Cosetta; Maccarinelli, Federica; Bianchi, Giada; Belotti, Angelo; Ribolla, Rossella; Favasuli, Vanessa; Revenko, Alexey S; MacLeod, Robert A; Willis, Brandon Stephen; Cai, Hongbo; Hauser, Joana; Rooney, Claire; Willis, Sophie Elizabeth; Martin, Philip L; Staniszewska, Anna Dominika; Ambrose, Helen; Hanson, Lyndsey; Cattaneo, Chiara; Tucci, Alessandra; Rossi, Giuseppe; Ronca, Roberto; Neri, Antonino; Mitola, Stefania; Bolli, Niccolo; Presta, Marco; Moschetta, Michele; Ross, Sarah; Roccaro, Aldo MSacco, Antonio; Federico, Cinzia; Todoerti, Katia; Ziccheddu, Bachisio; Palermo, Valentina; Giacomini, Arianna; Ravelli, Cosetta; Maccarinelli, Federica; Bianchi, Giada; Belotti, Angelo; Ribolla, Rossella; Favasuli, Vanessa; Revenko, Alexey S; Macleod, Robert A; Willis, Brandon Stephen; Cai, Hongbo; Hauser, Joana; Rooney, Claire; Willis, Sophie Elizabeth; Martin, Philip L; Staniszewska, Anna Dominika; Ambrose, Helen; Hanson, Lyndsey; Cattaneo, Chiara; Tucci, Alessandra; Rossi, Giuseppe; Ronca, Roberto; Neri, Antonino; Mitola, Stefania; Bolli, Niccolo; Presta, Marco; Moschetta, Michele; Ross, Sarah; Roccaro, Aldo