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Human recombinant bone morphogenetic protein 2 (rhBMP-2) accelerates bone regeneration but is associated with limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. This study assessed a new approach to the regeneration of the alveolar bone and periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication defective adenovirus to express the BMP-2 gene and pluronic F127 (PF127) in a large mammalian animal model. Bilateral maxillary periodontal defects were created over the premolar area in 9 mature male miniature swine. The 18 defects were randomly assigned to receive either BMP-2-expressing MSCs in the advBMP-2 group or MSCs alone in the MSC group. The regenerated periodontal attachment apparatus was evaluated histologically, and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis. Three months after implantation, significant bone volume was regenerated in the advBMP-2 group. Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. The use of ex vivo BMP-2-engineered autologous MSCs enhanced bone and periodontal apparatus regeneration in maxillary alveolar and periodontal defects in swine. This novel integrated approach might be suitable for clinical periodontal apparatus repair. This may be an alternative for cleft alveolar bone graft surgery.

Natural bone is comprised of nanosized blade-like crystals of hydroxyapatite grown in close contact with collagen (Col) fibers. Characteristics of artificial bone tissue differ considerably with those of natural ones, mainly from the unusual self-organizing interaction between the apatite crystals and the proteic components. Nanoparticle spheres of hydroxyapatite (n-HA), dispersed in reconstituted fibrous Col, were prepared in three weight ratios of 75:25, 65:35, and 50:50 (n-HA:Col). Bone marrow mesenchymal stem cells (MSCs) from rabbits were seeded and cultured on the n-HA/Col microbeads and characterized. n-HA were evenly distributed throughout the Col matrix and aggregated to microbeads as determined by scanning electron microscopy. Electron and confocal microscopy showed that the MSCs spread and attached to microbeads via focal adhesions, while staining for F-actin and DNA revealed the presence of stress fibers. The phenotype of the MSCs in the flow cytometry was identified as CD11a-, CD44+, and CD90.1+. The optimal weight ratio is 65:35 for the normalized alkaline phosphatase activities. The transduced MSCs, engineered by replication-defective adenovirus to express the BMP-2 gene, demonstrated synergic osteogenic effects in the microbeads. MSCs are capable of proliferating and differentiating in appropriate combinations of n-HA/Col. Thus it is a promising composite for future clinical applications.

The tourism industry is an indicator of the degree of internationalization and modernization of a country; and hotels are a key part in the tourism industry. According to studies on foreign tourists to Taiwan, expenses for international hotels make up the major portion of the tourists' total costs. Hence, international hotels play a significant role in the industry. The population for this study is 60 international hotels approved by the Taiwan Tourism Bureau. The sample is formed by 24 of these hotels. A questionnaire survey was conducted and 303 valid replies were received. The research analyzes cause and effect relationships among leader-member relations, as well as organizational commitment and job satisfaction utilizing structural equation modeling. The results show that job satisfaction is the mediating variable between organization commitment and leader-member relations.

Autologous vascularized bone grafts, allografts, and biocompatible artificial bone substitutes each have their shortcomings. Bones regenerated using recombinant human bone morphogenetic proteins, demineralized bone powder, or combinations of these are generally small and do not meet the need. The current trend is to use tissue engineering approaches with bone marrow mesenchymal stem cells (MSCs) to generate bones of a desired size and shape. A suspension of osteogenically induced MSCs (CD11a-, CD29+, CD44+) was added to 2% alginate, gelled by mixing this combination with calcium sulfate (CaSO(4) 0.2 g/mL), and injected into the subcutaneous pocket in the dorsal aspect of nude mice. Cells of various concentrations (0, 10, 50, and 70 million/mL) were used. These implanted constructs were harvested at predetermined times up to 30 weeks for histology. The doubling time of bovine MSCs is 3.75 +/- 1.96 days and the proliferation is rapid. Histological evaluation revealed signs of endochondrosis with woven bone deposition. The equilibrium modulus increased with time in vivo, though less than that of normal tissue. Implants seeded with 70 million cells/mL for 6 months resulted in the best formation of equilibrium modulus. This approach has several advantages: (i) obtaining MSCs is associated with low donor morbidity; (ii) MSCs proliferate rapidly in vitro, and a large number of viable cells can be obtained; and (iii) the MSC/alginate constructs can develop into bone-like nodules with high cell viability. Such a system may be useful in large-scale production of bony implants or in the repair of bony defects. The fact that endochondral bone formation led to woven bone suggests its potential feasibility in regional cell therapy.

Background Bone grafts, allografts, and biocompatible artificial bone substitutes all have their shortcomings when used for the repair of cranial bone defects. Tissue engineered bone shows promise as an alternative for the repair of these defects. Materials and methods Rabbit bone marrow mesenchymal stromal cells (MSCs) were separated from iliac crest aspirates and expanded in a monolayer culture 1 month before implantation. These MSCs were then infected with replication-defective adenovirus-human BMP-2 genes 1 week before implantation. Bilateral critical-size cranial defects were created in the animal with removal of osteoinductive periosteum and dura. MSCs were mixed with alginate UP (ultrapure) to form MSC/polymer construct. MSCs used for the control site were infected with adenovirus β-galactosidase (β-gal). After 1 week, 6 weeks, and 3 months, five rabbits from each experimental group were sacrificed and the cranial defect site was examined by histology study. Results Near-complete repair of the large size cranial defects using the tissue engineered MSC/alginate construct was observed. The H&E stain and von Kossa’s staining should better regenerate bone at the experiment site. A statistically significant difference in bone formation was noted by 3D CT imaging at 3 months post-BMP-2 treatment of the cranial defects (0.79 ± 0.06 versus 0.47 ± 0.05 cm 2 , P versus 0.33 ± 0.03 cm 2 , P = 0.347). Conclusions Near-complete repair of large cranial defects can be achieved using tissue engineered bone. The use of newly developed polymers as well as the integration of the stem cell concept with gene medicine is necessary to attain this goal.

The pathogenesis of necrotizing enterocolitis (NEC) is unknown. Ischemia and reperfusion (I/R) injury has been considered to be a major contributing factor. More recent reports have noted that apoptosis is a significant and perhaps the principal contributor to cell death after I/R. Some reports revealed that infants with NEC and perforated bowel can completely recover with drainage alone. This study aims to assess the ability of newborn rat intestine to resist apoptosis after I/R injury compared with adult rat intestine. Intestines from 10 groups of rats (n = 6 for each study group) were studied: (1) normal control group; (2) ischemia group, receiving vascular occlusion for 60 min; (3) I/R groups receiving vascular occlusion for 60 min and reperfusion for 15, 30, and 60 min, respectively. Apoptosis was quantified by TUNEL methods. Statistical analysis was performed using ANOVA with Dunn’s test. TUNEL-positive cells per 10 crypts were significantly increased in the ischemia and I/R groups compared to the control group. The peak number of positive cells by TUNEL was recognized 30 min after reperfusion in adult and newborn rats and then reduced gradually. The newborn rats had significantly less TUNEL-positive cells per 10 crypts than adult rats subjected to I/R injury (p < 0.05). We demonstrated that the activation of apoptosis occurred after intestinal I/R injury, especially during the reperfusion phase. The newborn intestine was more resistant to I/R injury and thus may have significant clinical application.

The occurrence of allergic rhinitis (AR) may be significantly influenced by air pollution. This study examined the association between the first occurrence of AR in preschool children and the pre-incident levels of air pollutants in Taiwan. We identified 9960 eligible subjects from a systematic sampling cohort database containing 400,000 insureds of the National Health Insurance from 2007 to 2011 and matched them with the environmental monitoring data from 2006 to 2011 according to the locations of their clinics. Pre-incident levels were determined using the average concentrations of air pollutants one or two weeks prior to the AR diagnoses. Logistic regression analyses were performed to determine any significant relationships between AR and specific air pollutants. The first AR incidence for Taiwanese preschool children, which increased with age, was 10.9% on average; boys appeared to have a higher percentage (14.2%) than girls (8.27%). Among the air pollutants, carbon monoxide (CO) and nitrogen oxides (NOX) were significantly related to AR after adjusting for age and gender (p < 0.05). Because both pollutants are considered to be traffic emissions, this study suggests that traffic emissions in Taiwan need to be controlled to lower the prevalence of children’s AR.

Background Mandibular bone regeneration is stepped up by human recombinant bone morphogenetic protein 2 (BMP-2) whose application is also related to limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. The alveolar bone grafting without traditional autologous bone grafts remains a challenge for plastic surgeons. Methods Bilateral mandibular alveolar and periodontal defects were created over the premolar areas in 9 mature male beagles. The defects were randomly assigned for either the adenovirus BMP-2 (advBMP-2) group with BMP-2-expressing mesenchymal stem cells (MSCs) or the control with MSCs alone. The regenerated periodontal attachment apparatus was evaluated histologically, and the whole regenerated bone volume was scrutinized from three-dimensional computed tomography analysis. Results Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. Eight weeks after implantation, the advBMP-2 group showed significant increase in bone regeneration than the control one. Conclusions Thus, the use of ex vivo BMP-2-engineered autologous MSCs boosted bone and periodontal apparatus regeneration in mandibular periodontal defects. This de novo approach might be suitable for clinical mandibular bone repair and periodontal apparatus repair.

Despite a wide range of available sources for bone repair, significant limitations persist. To bioengineer bone, we have previously transferred adenovirus-mediated human BMP-2 gene into autologous bone marrow stromal cells (MSC). We have successfully repaired large, full thickness, cranial defects using this approach. We report now the effectiveness of various hydrogels as the scaffold for this type of bone regeneration, comparing specifically alginate with Type I collagen. Cultured MSC of miniature swine were infected with BMP-2 or beta-gal adenovirus 7 days before implantation. These cells were mixed with alginate, ultrapure alginate, alginate-RGD, or type I collagen to fabricate the MSC/biomaterial constructs. The results of cranial bone regeneration were assessed by gross examination, histology, 3D CT, and biomechanical tests at 6 weeks and 3 months after implantation. We found that the BMP-2 MSC/collagen type I construct, but not the beta-gal control, effectively achieved nearly complete repair of the cranial defects. No bone regeneration was observed with the other hydrogels. Biomechanical testing showed that the new bone strength was very close and only slightly inferior to that of normal cranial bone. Controlling for the integration of stem cells and ex vivo gene transfer, the alginate scaffolds has a significant negative impact on the success of the construct. Our study demonstrates better bone regeneration by collagen type I over alginate. This may have therapeutic implications for tissue engineered bone repair.

Bone grafts, allografts, and biocompatible artificial bone substitutes all have their shortcomings when used for the repair of cranial bone defects. Tissue engineered bone shows promise as an alternative for the repair of these defects.Rabbit bone marrow mesenchymal stromal cells (MSCs) were separated from iliac crest aspirates and expanded in a monolayer culture 1 month before implantation. These MSCs were then infected with replication-defective adenovirus-human BMP-2 genes 1 week before implantation. Bilateral critical-size cranial defects were created in the animal with removal of osteoinductive periosteum and dura. MSCs were mixed with alginate UP (ultrapure) to form MSC/polymer construct. MSCs used for the control site were infected with adenovirus beta-galactosidase (beta-gal). After 1 week, 6 weeks, and 3 months, five rabbits from each experimental group were sacrificed and the cranial defect site was examined by histology study.Near-complete repair of the large size cranial defects using the tissue engineered MSC/alginate construct was observed. The HE stain and von Kossa's staining should better regenerate bone at the experiment site. A statistically significant difference in bone formation was noted by 3D CT imaging at 3 months post-BMP-2 treatment of the cranial defects (0.79 +/- 0.06 versus 0.47 +/- 0.05 cm(2), P0.001) but not at 6 weeks (0.36 +/- 0.04 versus 0.33 +/- 0.03 cm(2), P = 0.347).Near-complete repair of large cranial defects can be achieved using tissue engineered bone. The use of newly developed polymers as well as the integration of the stem cell concept with gene medicine is necessary to attain this goal.