In order to evaluate the repair potential in large osteochondral defects on high load-bearing sites, a hybrid scaffold system was made of three-dimensional porous Polycaprolactone (PCL) scaffold for the cartilage and tricalcium phosphate-reinforced PCL for the bone portion. Osteochondral defects of 4-mm diameter x 5.5-mm depth were created in the medial femoral condyle of adult New Zealand White rabbits. The defects were treated with hybrid scaffolds without cells (control group) or seeded with allogenic bone marrow-derived mesenchymal stem cells (BMSC) in each part (experimental group) by press-fit implantation. Implanted cells were tracked using Adeno-LacZ labeling. Repair tissues were evaluated at 3 and 6 months after implantation. Overall, the experimental group showed superior repair results as compared to the control group using gross examination, qualitative and quantitative histology, and biomechanical assessment. With BMSC implantation, the hybrid scaffolds provided sufficient support to new osteochondral tissues formation. The bone regeneration was consistently good from 3 to 6 months with firm integration to the host tissue. Cartilage layer resurfacing was more complicated. All of the samples showed cartilage tissues mixed with PCL scaffold filaments at 3 months. Histology at 6 months revealed some degradation phenomenon in several samples whereas others had a good appearance; however, the Young's moduli from the experimental group (0.72 MPa) approached that of normal cartilage (0.81 MPa). In vivo viability of implanted cells was demonstrated by the retention for 6 weeks in the scaffolds. This investigation showed that PCL-based hybrid scaffolds with BMSC may be an alternative treatment for large osteochondral defects in high-loading sites.
A fibrous scaffold made of alginate or alginate/chitosan was fabricated for annulus fibrosus (AF) cell culture using a wet-spinning and lyophilization technique. The scaffolds were evaluated using several in vitro tests. Scanning electron microscopy showed the scaffold fibers generally aligned in one direction with individual fiber diameters varying between 40-100 microm. The alginate/chitosan hybrid scaffold exhibited a slower degradation rate, while both scaffold types did not display any cyto-toxicity to 3T3 fibroblasts and could maintain canine AF cell growth. The AF cells retained their spherical shape within the fibrous scaffold at the beginning of the culture period and formed into cell clusters at later times. Specific extracellular matrix molecules, including collagen I, collagen II, and aggrecan, could be detected in the AF cell clusters. These results demonstrate the feasibility of using this hybrid alginate/chitosan scaffold for AF cell culture, and the potential application for intervertebral disc tissue engineering.
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The results of this study suggest that stress deprivation may be one contributor to the progression of tendinopathy in AT and SST, where the tendon designed for the lower in vivo loading demand (SST) was the most affected by a change in mechanical loading. The unique upregulation of MMP-13 with hydrostatic compression supports the impingement injury theory for rotator cuff tears.
BACKGROUND: 4-Hydroxyphenyl pyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the important target enzymes used to address the issue of weed control. HPPD-inhibiting herbicides can reduce the carotenoid content in plants and hinder photosynthesis, eventually causing albinism and death. Exploring novel HPPD-inhibiting herbicides is a significant direction in pesticide research. In the process of exploring new high-efficiency HPPD inhibitors, a series of novel quinoxaline derivatives were designed and synthesized using an active fragment splicing strategy. RESULTS: The title compounds were unambiguously characterized by infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectroscopy. The results of the in vitro tests indicated that the majority of the title compounds showed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD). Preliminary bioevaluation results revealed that a number of novel compounds displayed better or excellent herbicidal activity against broadleaf and monocotyledonous weeds. Compound III-5 showed herbicidal effects comparable to those of mesotrione at a rate of 150 g of active ingredient (ai)/ha for post-emergence application. The results of molecular dynamics verified that compound III-5 had a more stable protein-binding ability. Molecular docking results showed that compound III-5 and mesotrione shared homologous interplay with the surrounding residues. In addition, the enlarged aromatic ring system adds more force, and the hydrogen bond formed can enhance the synergy with π-π stacking.CONCLUSIONS: The present work indicates that compound III-5 may be a potential lead structure for the development of new HPPD inhibitors.
There is growing acceptance of traditional Chinese medicines (TCMs) as potential sources of clinical agents based on the demonstrated efficacies of numerous bioactive compounds in TCM extracts, such as paclitaxel, camptothecin and artemisinin.
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