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Restoring adequate blood supply is essential to the success of bone repair and augmentation procedures in craniofacial surgery. Nevertheless, the manner by which the incorporation of collagen gels (which can potentially induce angiogenesis), particulated deproteinized bovine bone grafts, or a combination of both can accelerate or delay bone regeneration in a clinical setting remains controversial. The objective of this study was to evaluate radiographically and histologically the capacity and functionality of particulated bone grafts and collagen gels on bone ossification and soft tissue formation in a rabbit calvarial defect. Bilateral calvarial defects in adult white New Zealand rabbits were filled or left either unfilled with bone grafts (DBBM), collagen gels (Gel), or a combination of both (DBBM + Gel). The defects were allowed to heal for 1, 2, and 6 months postoperatively before termination. Healing and regeneration patterns were assessed by 3D µCT and histological methods, and the biomechanical properties of regenerated tissue constructs were investigated and compared with autogenous calvarial bone. Results show that implanted DBBM and DBBM + Gel significantly enhanced immature bone formation compared with the empty and Gel groups; the latter treatment improved soft tissue formation and impeded immature bone formation but yielded no significant effect on mature bone formation. Implantation of DBBM not only effectively reconstructed 188.83 ± 25.25% of the tissue volume of the original defect, but it also regenerated bone tissue with similar tissue composition and biomechanical properties as the original autogenous bone. We also show that implanting different biomaterials can control the composition of soft and hard tissue in reconstructed tissue constructs in calvarial bone defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 529-544, 2019.

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Timely tissue vascularization and integration of engineered tissues into a patient plays an important role in the successful translation of engineered tissues into clinically relevant therapies. To decrease the time needed to vascularize an engineered adipose tissue, suitable local microenvironments provided by hydrogels to support cell-based functional vascular network formation have been investigated. Using the same biomolecule in solution, two types of hydrogels can be obtained: a "physical hydrogel" which is thermal-induced self-assemble fibril initiation and growth, due to amino and carboxyl telopeptides on collagen chains, and a "chemical hydrogel" which results from the covalently cross-linking of the side chains induced by one step enzyme mediation in aqueous solution. In this paper, we compare the capability of engineering vascular network and large-sized vascularized adipose tissue in vivo in different types of collagen hydrogels, physical and chemical crosslinking. The relationships between vascular network formation and hydrogel properties for the two types of hydrogels are discussed. Finally, we successfully engineered a vascularized adipose tissue construct (∼877.6 adipocytes/mm2; 94% area of a construct) in the absence of exogenous cytokines in chemical covalently crosslinking cell-laden hydrogel. These results show manipulating the polymerized methods of a hydrogel could not only modulate vascular network formation, but also regenerate adipose tissue in vivo.

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BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised the susceptibility breakpoints of cephalosporins for Enterobacteriaceae in 2010 and 2011. However, there is a lack of clinical data about the correlation of minimum inhibitory concentrations (MICs) and clinical outcome. Data for the distribution of MICs and clinical outcomes were analyzed in this study to evaluate the impact of changes in the CLSI breakpoints on the treatment of Klebsiella pneumoniae bacteremia. METHODS: Ninety-seven bacteremic K. pneumoniae isolates from Taichung Veterans General Hospital, Taichung, Taiwan were collected for study during the period 2009-2011. The cefazolin MIC was determined by the broth microdilution method according to the recommendations of the CLSI. The MIC distribution of cefazolin and the clinical responses to definitive cefazolin treatment were analyzed. RESULTS: The modal cefazolin MIC among the 97 isolates was 1 µg/mL and accounted for 73 (75.3%) isolates. There were 18 (18.6%) isolates with a cefazolin MIC of 2 µg/mL. The conventional dosage regimens of cefazolin (1 g every 6 hours or 8 hours) achieved a clinical cure in 70 (97.2%) of 72 patients in the group with a cefazolin MIC ≤1 µg/mL and in 14 (87.5%) of 16 patients in the group with a cefazolin MIC of 2 µg/mL. With the conventional dose, the cumulative clinical cure rate for K. pneumoniae bacteremia with cefazolin MIC ≤2 µg/mL was 95.5% (84/88 patients). CONCLUSION: The conventional cefazolin dose still can result in satisfactory clinical cure rates for bacteremic episodes due to K. pneumoniae with cefazolin MIC ≤2 µg/mL, the revised susceptible breakpoint of CLSI 2011.

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Graphene and its functionalized derivatives have recently emerged as interesting nanomaterials with promising applications in biomedicine. In this study, the long-term in vivo biodistribution of intravenously injected nanographene oxide (NGO) functionalized with poly sodium 4-styrenesulfonate (PSS) was systematically examined and the potential toxicity over 6 months of NGO-PSS nanoparticles was investigated. Our results showed that the nanoparticles mainly accumulate in the lung, liver and spleen, where they persist for at least 6 months. These nanoparticles result in acute liver injury and chronic inflammation of the lung, liver and spleen, as evidenced by blood biochemistry results and histological examinations.

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To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

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The animals used in liver fibrosis studies must usually be sacrificed. Ultrasound has been demonstrated to have the ability to diagnose hepatic fibrosis and cirrhosis in experimental small-animal models. However, few studies have used high-frequency ultrasound (HFU, 40 MHz) to monitor changes in the rat liver and other hollow organs longitudinally. In this study, liver fibrosis was induced by administering dimethylnitrosamine (DMN) in SD rats, aged 8 weeks, for three consecutive days per week for up to 4 weeks. A Chinese herbal medicine Yi Guan Jian (YGJ) was orally administered (1.8 g/kg daily) to DMN-induced liver fibrosis rats for 2 weeks. Compared with the normal control rats, rats treated with DMN for either 2 weeks or 4 weeks had significantly lower body weights, liver indexes and elevation of hydroxyproline, GOT, and GPT contents. YGJ herbal treatment remarkably prevented rats from DMN-induced liver fibrosis. The HFU scoring results among the normal controls, 2-week DMN-treated rats, 4-week DMN-treated rats, and combined 2-week YGJ therapy with 4-week DMN-treated rats also reached statistical significance. Thus, HFU is an accurate tool for the longitudinal analysis of liver fibrosis progression in small-animal models, and the YGJ may be useful in reversing the development of hepatic fibrosis.

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Treadmill running is a commonly used training method for patients with spasticity to improve functional performance. Botulinum toxin has been widely used therapeutically to reduce contraction force of spastic muscle. However, the effects of treadmill running in neuromuscular junction expression and motor unit physiology on muscle following botulinum toxin injection are not well established. To assess the effects of treadmill running on neuromuscular recovery of gastrocnemius following botulinum toxin A (BoNT-A) injection, we observed changes in gene expression. We hypothesized that the expression of acetylcholine receptor (AChR), myogenesis, and nerve plasticity could be enhanced. Twenty-four Sprague-Dawley rats received botulinum toxin injection in right gastrocnemius and were then randomly assigned into untrained control and treadmill running groups. The rats assigned to the treadmill running group were trained on a treadmill 3 times/week with a running speed of 15 m/min for 8 weeks. The duration of training was 20 min per session. Muscle strength and gene expression of AChR subunit (α, ß, δ, γ, and ε), MyoD, Myf-5, MRF4, myogenin, p21, IGF-1, GAP43, were analyzed. Treadmill running had no influence on gastrocnemius mass, but improved the maximal contraction force of the gastrocnemius in the treadmill running group (p < 0.05). Upregulation of GAP-43, IGF-1, Myo-D, Myf-5, myogenin, and AChR subunits α and ß were found following treadmill running. The expression of genes associated with neurite and AChR regeneration following treadmill exercise was upregulated, which may have contributed to enhanced recovery of gastrocnemius strength.

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AIMS: The purposes of this study were to examine the associations among social support, poststroke depression and quality of life among patients with first-time ischemic stroke and to further test the impact of the dimensions of social support on poststroke depression and quality of life. The proposed models included mediation hypotheses to examine the mediating roles of social support. BACKGROUND: Although considerable attention has recently been devoted to explaining why poststroke depression and poor quality of life are frequent concomitants of stroke, little empirical work has been conducted to test predictions based on these models, especially in Taiwan. DESIGN: A cross-sectional, descriptive correlation design was used. METHODS: The 102 patients with first-time ischemic stroke aged 32-90 (mean = 64.5, SD 11.8) were recruited from a large general hospital in Taiwan and through face-to-face survey interviews. The participants were assessed using the Social Support Inventory, Centre for Epidemiologic Studies Depression Scale, Barthel Index, the Instrumental Activities of Daily Living and Quality of Life Index-Stroke Version. The models were tested and confirmed through the application of structural equations with proposed variables. RESULTS: Nearly half of the Taiwanese patients with stroke felt depressed. Social support fully mediated the prediction of quality of life by age and partially mediated the prediction of quality of life by functional ability. Social support partially mediated the prediction of poststroke depression by functional ability. CONCLUSION: This study provides researchers and nurses with increased understanding of the mediating role of social support between functional ability and poststroke depression/quality of life. Social support may be a promising intervening variable in stroke outcome. RELEVANCE TO CLINICAL PRACTICE: The results suggest several clinical implications. The inclusion of social support in poststroke depression and quality of life after stroke may help nurses in planning stroke programme development, patient education, effective and efficient use of health care resources and effective rehabilitation, especially in those individuals who lack support or who are involved in stressful situations.

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