Thiol-norbornene photo-click hydrogels for tissue engineering applications.

Thiol-norbornene (thiol-ene) photo-click hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are cross-linked through light mediated orthogonal reactions between multi-functional norbornene-modified macromers (e.g., poly(ethylene glycol), hyaluronic acid, gelatin) and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, bis-cysteine peptides) using low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without additional co-initiator or co-monomer. The cross-linking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned owing to the orthogonal reactivity between norbornene and thiol moieties. Uniquely, the cross-linking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited, therefore the gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels using similar gelation conditions. These hydrogels have been prepared as tunable substrates for 2D cell culture, as microgels or bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for 3D cell culture. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, as well as cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel cross-linking and degradation mechanisms, tunable material properties, as well as the use of thiol-norbornene hydrogels in drug delivery and tissue engineering applications

Thiol-ene hydrogels as desmoplasia-mimetic matrices for modeling pancreatic cancer cell growth, invasion, and drug resistance

The development of pancreatic ductal adenocarcinoma (PDAC) is heavily influenced by local stromal tissues, or desmoplasia. Biomimetic hydrogels capable of mimicking tumor niches are particularly useful for discovering the role of independent matrix cues on cancer cell development. Here, we report a photo-curable and bio-orthogonal thiol-ene (i.e., cross-linked by mutually reactive norbornene and thiol groups via photoinitiation) hydrogel platform for studying the growth, morphogenesis, drug resistance, and cancer stem cell marker expression in PDAC cells cultured in 3D. The hydrogels were prepared from multi-arm poly(ethylene glycol)-norbornene cross-linked with protease-sensitive peptide to permit cell-mediated matrix remodeling. Collagen 1 fibrils were incorporated into the covalent network while cytokines (e.g., EGF and TGF-β1) were supplemented in the culture media for controlling cell fate. We found that the presence of collagen 1 enhanced cell proliferation and Yes-associated protein (YAP) translocation to cell nuclei. Cytokines and collagen 1 synergistically up-regulated MT1-MMP expression and induced cell spreading, suggestive of epithelial-mesenchymal transition (EMT) in the encapsulated cells. Furthermore, PDAC cells cultured in 3D developed chemo-resistance even in the absence of collagen 1 and cytokines. This phenotype is likely a consequence of the enrichment of pancreatic cancer stem cells that expressed high levels of CD24, sonic hedgehog (SHH), and vascular endothelial growth factor (VEGF)

Anatomic variations of the T2 nerve root (including the nerve of Kuntz) and their implications for sympathectomy

AbstractObjective: The aim of this study was to clarify the anatomic variations of the intrathoracic nerve of Kuntz, and this should help delineate the resection margins during video-assisted thoracic sympathectomy. Methods: Sixty-six thoracic sympathetic chains of 39 adult Korean cadavers were dissected on both sides of the thorax in 27 cadavers (54 sides) and on one side in 12 cadavers (12 sides). Results: The intrathoracic nerve was observed in 45 (68.2%) sides and was present bilaterally in 48.1% of cadavers. No intrathoracic nerve or ascending ramus communicans arising from the second thoracic nerve was observed in only 5 (7.6%) sides. The diameter of the intrathoracic nerve was 1.25 ± 0.55 mm on average. The arising point of the intrathoracic nerve from the second thoracic nerve was 7.3 mm on average from the sympathetic trunk. Presence of the stellate ganglion was noted in 56 (84.8%) sides, and 6 (9.1%) sides showed a single large ganglion formed by the stellate and the second thoracic sympathetic ganglia. The second thoracic sympathetic ganglion was most commonly located (50%) in the second intercostal space. Conclusion: The anatomic variations of the intrathoracic nerve of Kuntz and the second thoracic sympathetic ganglion were characterized in human cadavers. It is hoped that this study will help to improve the recurrence of symptoms caused by the intrathoracic nerve in an upper thoracic sympathectomy for hyperhidrosis.J Thorac Cardiovasc Surg 2002;123:498-50

Performance-Based Evaluation of a Double-Deck Tunnel and Design Optimization

The double-deck tunnel is well known as smart infrastructure because multiple sections can be used for various purposes. Although the stability of a double-deck tunnel is mainly governed by the intermediate slab, the effect of various governing factors on tunnel structural stability has not been fully investigated. In this study, performance-based evaluation method for a double-deck tunnel is suggested as a three-dimensional matrix considering the life cycle of a double-deck tunnel. Moreover, a customized software for design and maintenance of a double-deck tunnel is developed. A structural analysis solver based on a beam–spring model for a double-deck tunnel was embedded in this code. The effects of connection type as well as depth of tunnel, ground stiffness and traffic load on structural behavior of tunnel were investigated. From the analysis, it was found that the connection type between segment lining and intermediate slab significantly affects the behavior of segment lining: simply connected condition causes lesser stress and moment than fully fixed condition. The deeper the tunnel depth, the greater the member force of segment lining. In addition, as both the tunnel depth and the ground stiffness increase, the influence of connection type on the structural stability of the double-deck tunnel becomes insignificant