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Antibiotic beads can be used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, the osteogenic enhancer lithium chloride (LiCl), and hot compression to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was used to characterize in vitro release characteristics of vancomycin and Li over a 42-day period. The release profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium cotreatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased the mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the distal femoral cavities of rabbits, and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and the vancomycin concentrations were much greater than the breakpoint sensitivity. Four rabbits in each group were sacrificed at 8 weeks for histological observation. More mature bone tissue was observed in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections. [ABSTRACT FROM AUTHOR]

This study develops a composite bone graft of CaO–MgO–SiO2 glass–ceramic and CaSO4 [abbreviated as (CMS)3−x(CS)x] via the sponge replication technique with weight fractions of x = 0, 1, 1.5, 2, and 3. The (CMS)1.5(CS)1.5 composite displays a superior degradability and, a suitable compressive strength of ∼3 MPa, and excellent cell proliferation and differentiation. The in vivo rat femur test in the hybrid-pore (CMS)1.5(CS)1.5 composite granules achieves a higher rate of bone formation, which is ∼2.7 times better than that of the commercial HAP/β-TCP at 12 weeks. Improved expressions of osteocyte and mature osteocyte marker genes, namely (Spp1, Dmp1, and Fgf23), were observed in the (CMS)1.5(CS)1.5 group, indicating a faster differentiation into mature bone tissue. The ions release of (CMS)1.5(CS)1.5 through the ERK1/2 signaling pathway promotes osteogenic differentiation. The high bone generation rate can be attributed to faster active ions release and modified surface topography. This work highlights an excellent bone graft candidate for clinical applications in orthopedic surgery. [ABSTRACT FROM AUTHOR]

The high prevalence of kidney diseases and the low identification rate of drug nephrotoxicity in preclinical studies reinforce the need for representative yet feasible renal models. Although in vitro cell-based models utilizing renal proximal tubules are widely used for kidney research, many proximal tubule cell (PTC) lines have been indicated to be less sensitive to nephrotoxins, mainly due to altered expression of transporters under a two-dimensional culture (2D) environment. Here, we selected HK-2 cells to establish a simplified three-dimensional (3D) model using gelatin sponges as scaffolds. In addition to cell viability and morphology, we conducted a comprehensive transcriptome comparison and correlation analysis of 2D and 3D cultured HK-2 cells to native human PTCs. Our 3D model displayed stable and long-term growth with a tubule-like morphology and demonstrated a more comparable gene expression profile to native human PTCs compared to the 2D model. Many missing or low expressions of major genes involved in PTC transport and metabolic processes were restored, which is crucial for successful nephrotoxicity prediction. Consequently, we established a cost-effective yet more representative model for in vivo PTC studies and presented a comprehensive transcriptome analysis for the systematic characterization of PTC lines. [ABSTRACT FROM AUTHOR]

Background: Alveolar bone and cementum share many biological and developmental similarities. The mineralizing effect of calcitriol has been previously reported. Yet, its cemento-inductivity has not been confirmed. This study evaluated the potential cemento-inductivity effect of calcitriol and enamel matrix derivative (EMD) on human periodontal ligament-derived cells (hPDLCs).Methods: The hPDLCs obtained from extracted third molars or premolars were cultured with calcitriol, or EMD. Cementogenic gene expression was examined using real-time quantitative reverse transcription polymerase chain reaction. Expression analysis also included cementoblast-specific markers, cementum protein 1 (CEMP1), cementum attachment protein (CAP), and recently reported cementoblast-enriched genes, secreted frizzled related protein 1 (SFRP1), and Dickkopf-related protein 1 (DKK1). Mineralization capacities were evaluated by alkaline phosphatase (ALP) activity, Alizarin Red, and Von Kossa staining followed by scanning electron microscope imaging and element mapping.Results: Among tested conditions, 10 nM calcitriol enhanced most cementogenic gene expression, transforming growth factor-β1, bone morphogenetic proteins (BMP-2 and BMP-4), core-binding factor subunit alpha-1/Runt-related transcription factor 2, Type I collagen, ALP, bone sialoprotein, osteopontin), osteocalcin, CEMP1, and CAP, and Wnt signaling negative modulators, SFRP1 and DKK1, along with highest ALP activity and mineralization formation in hPDLCs. However, only moderate CEMP1 protein was observed. In contrast, EMD stimulated stronger CEMP1 and CAP protein, but presented weaker mineralization capacity, hinting at the possibility that strong stimulation of mineralization might dominate cemetogenic specific factors and vice versa.Conclusions: Calcitriol demonstrated not only great osteoinductivity, but also the potential to induce cementogenic gene expression by initiating hPDLC differentiation and promoting mineralization. Compared with calcitriol, EMD promoted cemento-inductivity in hPDLCs at a later time point via highly expressed CEMP1 and CAP protein, but with less mineralization. Thus, calcitriol and EMD could provide differential enhancement of cemento-induction and mineralization, likely acting at various differentiation stages. [ABSTRACT FROM AUTHOR]

Closed-incision negative-pressure wound therapy (iNPWT) is known to enhance wound healing and tissue regeneration. The main aim of the present study is to investigate its effectiveness on enhancing wound healing under tension. An animal study was designed using a swine model by removing a skin flap to create a wound that could be closed primarily under tension, and iNPWT was applied. The enhancement of angiogenesis, lymphangiogenesis, collagen deposition, and tissue proliferation with reduced inflammation by iNPWT was confirmed by histology. The effect of iNPWT was further verified in patients receiving a profunda artery perforator (PAP) free flap for breast reconstruction. iNPWT was applied on the transversely designed donor site in continuous mode for 7 days, in which the wound was always closed under tension. A significant improvement in off-bed time was noted with the application of iNPWT (4.6 ± 1.1st and 5.5 ± 0.8th postoperative days in the iNPWT and control groups, respectively, p = 0.028). The control group (without iNPWT treatment) presented more cases of poor wound healing in the acute (23.1% vs. 0%) and wound breakdown in the late (23.1% vs. 8.3%) stages. The treatment of closed incisions under tension with iNPWT clinically enhances wound healing and tissue regeneration and with histological evidence. [ABSTRACT FROM AUTHOR]

We have deleted a gene for a sensor histidine kinase, dspA (or hik33), in the cyanobacterium Synechocystis sp. strain PCC6803. In low and moderate light, the mutant grew slowly under photoautotrophic conditions, with a doubling time of ~40 h, and had severely reduced photosynthetic oxygen evolution. When the mutant was maintained in low or moderate light in the presence of glucose, its growth rate was only somewhat lower than that of wild-type cells. However, the mutant was light sensitive and rapidly died in high light. Furthermore, levels of many transcripts encoding genes associated with photosynthesis were altered in the mutant relative to wild-type Synechocystis sp. strain PCC6803 both in low light and following exposure to high light. There was constitutive expression of several high-light-inducible genes, including hli, psbAIII, and gpx2; there was little increased accumulation of sodB mRNA in high light; and the cells failed to accumulate gpx; and psaAB mRNAs in low light in the presence of glucose, although a normal decline in the levels of these mRNAs was observed during exposure to high light. These results suggest that DspA is involved in controlling sets of photosynthetic and high-light-responsive genes, either directly or indirectly. These and other results, some of which are presented in a companion paper (C.-J. Tu, J. Shrager, R. Burnap, B. L. Postier, and A. R. Grossman, J. Bacteriol. 186:3889-3902, 2004), suggest that DspA acts as a global regulator that helps coordinate cellular metabolism with growth limitations imposed by environmental conditions.

The clinical demand for cartilage tissue engineering is potentially large for reconstruction defects resulting from congenital deformities or degenerative disease due to limited donor sites for autologous tissue and donor site morbidities. Cartilage tissue engineering has been successfully applied to the medical field: a scaffold pre-cultured with chondrocytes was used prior to implantation in an animal model. We have developed a surgical approach in which tissues are engineered by implantation with a vascular pedicle as an in vivo bioreactor in bone and adipose tissue engineering. Collagen type II, chitosan, poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were four commonly applied scaffolds in cartilage tissue engineering. To expand the application of the same animal model in cartilage tissue engineering, these four scaffolds were selected and compared for their ability to generate cartilage with chondrocytes in the same model with an in vivo bioreactor. Gene expression and immunohistochemistry staining methods were used to evaluate the chondrogenesis and osteogenesis of specimens. The result showed that the PLGA and PCL scaffolds exhibited better chondrogenesis than chitosan and type II collagen in the in vivo bioreactor. Among these four scaffolds, the PCL scaffold presented the most significant result of chondrogenesis embedded around the vascular pedicle in the long-term culture incubation phase. [ABSTRACT FROM AUTHOR]

This study develops a composite bone graft of CaO-MgO-SiO 2 glass-ceramic and CaSO 4 [abbreviated as (CMS) 3- x (CS) x ] via the sponge replication technique with weight fractions of x = 0, 1, 1.5, 2, and 3. The (CMS) 1.5 (CS) 1.5 composite displays a superior degradability and, a suitable compressive strength of ∼3 MPa, and excellent cell proliferation and differentiation. The in vivo rat femur test in the hybrid-pore (CMS) 1.5 (CS) 1.5 composite granules achieves a higher rate of bone formation, which is ∼2.7 times better than that of the commercial HAP/β-TCP at 12 weeks. Improved expressions of osteocyte and mature osteocyte marker genes, namely (Spp1, Dmp1, and Fgf23), were observed in the (CMS) 1.5 (CS) 1.5 group, indicating a faster differentiation into mature bone tissue. The ions release of (CMS) 1.5 (CS) 1.5 through the ERK1/2 signaling pathway promotes osteogenic differentiation. The high bone generation rate can be attributed to faster active ions release and modified surface topography. This work highlights an excellent bone graft candidate for clinical applications in orthopedic surgery.