Fibroblast growth factors (FGFs) that signal through FGF receptors (FGFRs) regulate a broad spectrum of biological functions, including cellular proliferation, survival, migration, and differentiation. The FGF signal pathways are the RAS/MAP kinase pathway, PI3 kinase/AKT pathway, and PLCγ pathway, among which the RAS/MAP kinase pathway is known to be predominant. Several studies have recently implicated the in vitro biological functions of FGFs for tissue regeneration. However, to obtain optimal outcomes in vivo, it is important to enhance the half-life of FGFs and their biological stability. Future applications of FGFs are expected when the biological functions of FGFs are potentiated through the appropriate use of delivery systems and scaffolds. This review will introduce the biology and cellular functions of FGFs and deal with the biomaterials based delivery systems and their current applications for the regeneration of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve tissues.

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Background Mobile health (MH) technologies including clinical decision support systems (CDSS) provide an efficient method for patient monitoring and treatment. A mobile CDSS is based on real-time sensor data and historical electronic health record (EHR) data. Raw sensor data have no semantics of their own; therefore, a computer system cannot interpret these data automatically. In addition, the interoperability of sensor data and EHR medical data is a challenge. EHR data collected from distributed systems have different structures, semantics, and coding mechanisms. As a result, building a transparent CDSS that can work as a portable plug-and-play component in any existing EHR ecosystem requires a careful design process. Ontology and medical standards support the construction of semantically intelligent CDSSs. Methods This paper proposes a comprehensive MH framework with an integrated CDSS capability. This cloud-based system monitors and manages type 1 diabetes mellitus. The efficiency of any CDSS depends mainly on the quality of its knowledge and its semantic interoperability with different data sources. To this end, this paper concentrates on constructing a semantic CDSS based on proposed FASTO ontology. Results This realistic ontology is able to collect, formalize, integrate, analyze, and manipulate all types of patient data. It provides patients with complete, personalized, and medically intuitive care plans, including insulin regimens, diets, exercises, and education sub-plans. These plans are based on the complete patient profile. In addition, the proposed CDSS provides real-time patient monitoring based on vital signs collected from patients’ wireless body area networks. These monitoring include real-time insulin adjustments, mealtime carbohydrate calculations, and exercise recommendations. FASTO integrates the well-known standards of HL7 fast healthcare interoperability resources (FHIR), semantic sensor network (SSN) ontology, basic formal ontology (BFO) 2.0, and clinical practice guidelines. The current version of FASTO includes 9577 classes, 658 object properties, 164 data properties, 460 individuals, and 140 SWRL rules. FASTO is publicly available through the National Center for Biomedical Ontology BioPortal at https://bioportal.bioontology.org/ontologies/FASTO . Conclusions The resulting CDSS system can help physicians to monitor more patients efficiently and accurately. In addition, patients in rural areas can depend on the system to manage their diabetes and emergencies. Electronic supplementary material The online version of this article (10.1186/s12911-019-0806-z) contains supplementary material, which is available to authorized users.

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Dentin sialophosphoprotein (DSPP) is critical for dentin mineralization. However, the function of dentin sialoprotein (DSP), the cleaved product of DSPP, remains unclear. This study aimed to investigate the signal transduction pathways and effects of recombinant human DSP (rh-DSP) on proliferation, migration, and odontoblastic differentiation in human dental pulp cells (HDPCs). The exogenous addition of rh-DSP enhanced the proliferation and migration of HDPCs in dose- and time-dependent manners. rh-DSP markedly increased ALP activity, calcium nodule formation, and levels of odontoblastic marker mRNA. rh-DSP increased BMP-2 expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist, noggin. Furthermore, rh-DSP phosphorylated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), Akt, and IκB-α, and induced the nuclear translocation of the NF-κB p65 subunit. Analysis of these data demonstrates a novel signaling function of rh-DSP for the promotion of growth, migration, and differentiation in HDPCS via the BMP/Smad, JNK, ERK, MAPK, and NF-κB signaling pathways, suggesting that rh-DSP may have therapeutic utility in dentin regeneration or dental pulp tissue engineering.

Three-dimensional (3D) collagen hydrogels have been extensively used for cell culture experiments and are more closely representative of in vivo conditions than monolayer (2D) culture. Here we cultured rat bone marrow-derived mesenchymal stem cells (MSCs) in collagen hydrogels containing varying concentrations of basic fibroblast growth factor (bFGF) to examine the effect of bFGF on MSC proliferation and osteogenic differentiation in 3D culture. The optimal bFGF concentration that promoted the greatest degree of cell proliferation and expression of the early osteogenic induction marker alkaline phosphatase was also determined. Subsequent quantitative real-time polymerase chain reaction analysis of gene expression demonstrated that bFGF promoted significant upregulation of the bone-related genes: collagen type I, osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OCN) for periods of up to 21 days. Immunofluorescence staining and fluorescence-activated cell sorting analysis further supported the enhanced osteogenic differentiation of cells as a greater proportion of cells were found to express OPN. Matrix mineralization within the collagen hydrogels was enhanced in the presence of bFGF, as assessed by calcium detection using von Kossa staining. These results clearly demonstrate a positive effect of bFGF on proliferation and osteogenic induction of MSCs in 3D collagen hydrogels when applied at the appropriate concentration. Moreover, collagen hydrogel constructs containing MSCs and appropriate growth factor stimulus might be a potentially useful biological tool for 3D bone tissue engineering.

Human periodontal ligament stem cells (PDLSCs) from extracted third molar teeth are a type of adult stem cell originating from dental tissue. PDLSCs are known to have a self-renewal capacity and multi-lineage differentiation potential. Vascular endothelial growth factor (VEGF), an angiogenic/vasculogenic factor, has been shown to stimulate endothelial cell mitogenesis and cell migration. Another growth factor, fibroblast growth factor-2 (FGF-2), a mitogenic factor, enhances osteogenesis in mesenchymal stem cells (MSCs). This study examines the effects of VEGF and FGF-2 on PDLSCs in vitro and in vivo compared with those on bone marrow stem cells (BMSCs) as a positive control. Treatment of PDLSCs with VEGF increases the accumulation of calcium nodules, alkaline phosphatase (ALP) activity and the formation of hard tissue and up-regulates the mRNA level of runt-related transcription factor 2 (Runx2). In contrast, FGF-2 enhances the proliferation of PDLSCs in vitro in cell culture, where it significantly decreases calcium accumulation and ALP activity and down-regulates the expression of osteogenic gene markers (i.e., Runx2, ALP, type I collagen) involved in osteogenic induction. We have also transplanted PDLSCs with hydroxyapatite/tricalcium phosphate particles (HA/TCP) as carriers for each factor (VEGF, FGF-2) into nude mice and, after 8 weeks, observed the in vivo formation of hard tissue at the dorsal surface. Based on our results, we suggest that VEGF has positive effects on odonto-/osteogenic differentiation in vitro and on the formation of mineralized structure in vivo. FGF-2 might be a powerful promoter of the proliferation of progenitor cells in hard tissue regeneration but exogenous FGF-2 might inhibit terminal differentiation.