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| Supramolecular hydrogels inspired by collagen for tissue engineering.
May 27, 2010 at 6:24 AM
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| | Supramolecular hydrogels inspired by collagen for tissue engineering. Org Biomol Chem. 2010 May 26; Authors: Hu Y, Wang H, Wang J, Wang S, Liao W, Yang Y, Zhang Y, Kong D, Yang Z Supramolecular hydrogels are promising biomaterials for cell culture in 2-D and 3-D environments. Inspired by the chemical structure of collagen, which bears the repeating tripeptide of glycine-Xaa-4R-hydroxyproline (GXO; Xaa is any one of the natural amino acids), we designed and synthesized a small library of supramolecular hydrogelators (a total of 6). We found that four of the hydrogels were suitable for NIH 3T3 cell culture in the 2-D environments. Gel 2, the best hydrogel, has properties that are similar to those of collagen for 3T3 cell culture. These findings not only provide more supramolecular hydrogel candidates for tissue engineering, but also offer a new strategy for designing biomaterials that mimic nature. PMID: 20502821 [PubMed - as supplied by publisher] | | |
| Integrin-blocking antibodies delay keratinocyte re-epithelialization in a human three-dimensional wound healing model.
May 27, 2010 at 6:24 AM
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| | Integrin-blocking antibodies delay keratinocyte re-epithelialization in a human three-dimensional wound healing model. PLoS One. 2010;5(5):e10528 Authors: Egles C, Huet HA, Dogan F, Cho S, Dong S, Smith A, Knight EB, McLachlan KR, Garlick JA The alpha6beta4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, alpha6beta4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE), which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting beta4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different beta4 epitopes, one adhesion-blocking (ASC-8) and one non-adhesion blocking (ASC-3), and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where beta4 ! is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate beta4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process. PMID: 20502640 [PubMed - in process] | | |
| Generation of Two- and Three-Dimensional Lacrimal Gland Constructs.
May 27, 2010 at 6:24 AM
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| | Generation of Two- and Three-Dimensional Lacrimal Gland Constructs. Dev Ophthalmol. 2010;45:49-56 Authors: Schrader S, Liu L, Kasper K, Geerling G Aqueous tear deficiency due to lacrimal gland insufficiency is one of the major causes of dry eye. In severe cases, such as Sjoegren's syndrome, Stevens-Johnson syndrome or ocular cicatricial pemphigoid, therapy with artificial tears can be insufficient to relieve severe discomfort. Engineering a lacrimal gland construct may offer a suitable alternative transplant with a tear-like secretion. However, the reconstruction of a complex structure such as the lacrimal gland is challenging, and a lacrimal gland substitute must meet several criteria. It has to contain enough functional lacrimal gland cells to produce an adequate amount of tear fluid, and a suitable matrix is needed to deliver the cells to the patient. The growing field of regenerative medicine offers promising new prospects for lacrimal gland reconstruction. This article summarizes our group's current work in developing models for lacrimal gland reconstruction, and also discusses the perspectives of a tis! sue-engineered lacrimal gland for future applications. PMID: 20502026 [PubMed - as supplied by publisher] | | |
| The teaching of fixed partial dentures in undergraduate dental schools in Ireland and the United Kingdom.
May 27, 2010 at 6:24 AM
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| | The teaching of fixed partial dentures in undergraduate dental schools in Ireland and the United Kingdom. J Oral Rehabil. 2010 May 24; Authors: Lynch CD, Singhrao H, Addy LD, Gilmour AS Summary All areas of the practice of dentistry are evolving at a considerable pace. One area in particular which has seen a rapid revolution is the oral rehabilitation of partially dentate adults. The aim of this study was to describe the contemporary teaching of fixed partial dentures (FPDs) in dental schools in Ireland and the United Kingdom. An online questionnaire which sought information in relation to the current teaching of FPDs was developed and distributed to 15 Irish and UK dental schools with undergraduate teaching programmes in Spring 2009. Responses were received from 12 schools (response rate = 80%). All schools offer teaching programmes in relation to FPDs. The number of hours devoted to pre-clinical/phantom head teaching of FPDs ranged from 3 to 42 h (mean: 16 h). The staff/student ratio for pre-clinical teaching courses in FPDs ranged from 1:6 to 1:18 (mode: 1:12). Cantilever resin-retained FPDs were the most popular type of FPD provided clinicall! y (average = 0.83 per school; range = 1-2). Five schools (42%) report that they have requirements (e.g. targets, quotas, competencies) which students must complete prior to graduation in relation to FPDs. Fixed partial dentures form an important part of the undergraduate teaching programme in UK and Irish dental schools. While this teaching is subjected to contemporary pressures such as lack of curriculum time and a lack of available clinical facilities and teachers, there is evidence that teaching programmes in this area are evolving and are sensitive to current clinical practice trends and evidence-based practice. PMID: 20500547 [PubMed - as supplied by publisher] | | |
| [Reconstruction of osteochondral defects with a stem cell-based cartilage-polymer construct in a small animal model]
May 27, 2010 at 6:24 AM
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| | [Reconstruction of osteochondral defects with a stem cell-based cartilage-polymer construct in a small animal model] Z Orthop Unfall. 2010 Jan;148(1):31-8 Authors: Berner A, Siebenlist S, Reichert JC, Hendrich C, Nöth U AIM: Mesenchymal stem cells have a high therapeutic potential for the reconstruction of articular cartilage defects. In this study, a cartilage-polymer construct using mesenchymal stem cells from trabecular bone and a polylactic acid polymer was fabricated with a press-coating technique. We investigated whether cells from human trabecular bone fragments have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow and whether it is possible to reconstruct an osteochondral lesion in the nude rat with the fabricated construct. METHOD: Cells were obtained from the femoral head of patients undergoing total hip arthroplasty. The fabrication of the constructs was performed by centrifugation of 1.5x10(6) cells to a cell pellet which was then placed in a polymer block. The fabricated cell constructs were cultivated for 3 weeks in a serum-free medium, supplemented with transforming growth factor beta1. Every third day, the chondrog! enic differentiation was analysed using chondrogenic and osteogenic marker genes. After three weeks the constructs were implanted into 5 mm osteochondral defects of the knee joint of nude rats. After 4 and 12 weeks histochemical and immunohistochemical analyses were performed. RESULTS: At the end of the culture period the constructs showed a proteoglycan-rich extracellular matrix with the expression of collagen types II, IX and X as well as aggrecan und COMP (cartilage oligomeric matrix protein). No osteogenic markers except collagen type I could be detected. The analysis of the in vivo experiment showed a good defect filling with a reconstructed cartilage surface along with increasing resorption of the polymer. CONCLUSION: We have shown that it is possible to fabricate cartilage-polymer constructs from trabecular bone-derived cells, and that the cells have the same chondrogenic differentiation potential as mesenchymal stem cells derived from bone marrow. With the fabricate! d cartilage-polymer construct it is possible to reconstruct an! osteoch ondral defect in the knee joint of the nude rat. PMID: 20151353 [PubMed - indexed for MEDLINE] | | |
| [Novel software-based and validated evaluation method for objective quantification of bone regeneration in experimental bone defects]
May 27, 2010 at 6:24 AM
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| | [Novel software-based and validated evaluation method for objective quantification of bone regeneration in experimental bone defects] Z Orthop Unfall. 2010 Jan;148(1):19-25 Authors: Schönberger T, Kasten P, Fechner K, Südkamp NP, Pearce S, Niemeyer P AIM: The quantification of newly formed bone in experimental defect models is a problem in various experimental set-ups. Several methods have been described to evaluate and quantify the regeneration of newly formed bone in various animal models. Most methods only describe the amount of regenerated tissue on a semi-quantitative level, the results significantly depend on the subjective rating of the observer and such evaluation methods have not been validated in terms of objectivity and reliability. The aim of the present study was to introduce a novel evaluation method for the accurate quantification of bone regeneration on digital X-ray images using a freely available digital image software analysis programme (GIMP, GNU General Public Licence). METHODS: The method introduced here contains 5 steps: standardisation of size and colour, determination of range of interest (ROI), defining different qualities of mineralisation, pixel analysis with histogram function, sim! ilar to the Hondsfield index, and quantification. In order to evaluate the objectivity and reliability, the quantification method was compared to semi-quantitative scores described by Mosheiff and Werntz for inter- and intraobserver variability. Six observers were asked to determine bone regeneration in 16 X-ray images of 2 different animal models. In order to describe intraobserver variability, the evaluation was repeated after a period of 4 weeks. Statistical analysis including determination of intra- and interobserver variability (Bland-Altman coefficient of reproduction) was performed using SAS software. RESULTS: For both experimental set-ups analysed in this project (rabbit and sheep bone defects), the objectivity was significantly higher in the GIMP-based evaluation compared to the evaluation according to Mosheiff and Werntz using the Bland-Altman coefficient (rabbit: GIMP: 0.095, Mosheiff: 0.272, Werntz: 0.283; sheep: GIMP: 0.098, Mosheiff: 0.658, Werntz: 0.668). Ana! logous results were obtained for reliability (rabbit: GIMP: 0.! 086, Mos heiff: 0.221, Werntz: 0.385; sheep: GIMP: 0.102, Mosheiff: 0.339, Werntz: 0.623). CONCLUSION: This quantification method introduced here has proved to be a reliable and "easy-to-use" tool in order to perform objective quantification of bone regeneration in 2 different experimental set-ups. It offers a more detailed and quantitative way for precise determination of regenerated tissue and is characterised by higher objectivity and reliability compared to other semi-quantitative evaluation methods. The objectivity seems to be independent of the animal model to which the method is applied. PMID: 20135589 [PubMed - indexed for MEDLINE] | | |
| Inosculation: connecting the life-sustaining pipelines.
May 27, 2010 at 6:24 AM
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| | Inosculation: connecting the life-sustaining pipelines. Tissue Eng Part B Rev. 2009 Dec;15(4):455-65 Authors: Laschke MW, Vollmar B, Menger MD Recent progress in engineering microvascular networks in vitro and in vivo offers exciting opportunities to create tissue constructs with preformed blood vessels, which are rapidly blood perfused by developing interconnections to the preexisting blood vessels of the host tissue after implantation. This process, termed as inosculation, is well known from the revascularization of various tissue grafts, such as transplanted skin, nerves, or bone. It is characterized by the close interaction of the implant's preformed microvascular network and the host microvasculature. The sprouting angiogenic activity of both counterparts determines whether inosculation takes place internally within the implant or externally within the surrounding host tissue. Successful inosculation involves vascular remodeling as well as infiltration of inflammatory cells and stem cells. With the use of sophisticated in vitro and in vivo models, more detailed analysis of regulatory mechanisms of i! nosculation will help to develop novel strategies, aiming at further accelerating the establishment of a life-sustaining blood supply to implanted tissue constructs. PMID: 19552605 [PubMed - indexed for MEDLINE] | | |
| Micro- and nanoscale control of the cardiac stem cell niche for tissue fabrication.
May 27, 2010 at 6:24 AM
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| | Micro- and nanoscale control of the cardiac stem cell niche for tissue fabrication. Tissue Eng Part B Rev. 2009 Dec;15(4):443-54 Authors: Murtuza B, Nichol JW, Khademhosseini A Advances in stem cell (SC) biology have greatly enhanced our understanding of SC self-renewal and differentiation. Both embryonic and adult SCs can be differentiated into a great variety of tissue cell types, including cardiac myocytes. In vivo studies and clinical trials, however, have demonstrated major limitations in reconstituting the myocardium in failing hearts. These limitations include precise control of SC proliferation, survival and phenotype both prior and subsequent to transplantation and avoidance of serious adverse effects such as tumorigenesis and arrhythmias. Micro- and nanoscale techniques to recreate SC niches, the natural environment for the maintenance and regulation of SCs, have enabled the elucidation of novel SC behaviors and offer great promise in the fabrication of cardiac tissue constructs. The ability to precisely manipulate the interface between biopolymeric scaffolds and SCs at in vivo scale resolutions is unique to micro- and nanoscal! e approaches and may help overcome limitations of conventional biological scaffolds and methods for cell delivery. We now know that micro- and nanoscale manipulation of scaffold composition, mechanical properties, and three-dimensional architecture have profound influences on SC fate and will likely prove important in developing the next generation of "transplantable SC niches" for regeneration of heart and other tissues. In this review, we examine two key aspects of micro- and nanofabricated SC-based cardiac tissue constructs: the role of scaffold composition and the role of scaffold architecture and detail how recent work in these areas brings us closer to clinical solutions for cardiovascular regeneration. PMID: 19552604 [PubMed - indexed for MEDLINE] | | | | 
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