VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF) were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP) ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration.

Bone apposition to a titanium-zirconium alloy implant, as compared to two other titanium-containing implants

Implants made of commercially pure titanium (cpTi) are widely and successfully used in dentistry. For certain indications, diameter-reduced Ti alloy implants with improved mechanical strength are highly desirable. The aim was to compare the osseointegration of titanium-zirconium (TiZr) and cpTi implants with a modified sandblasted and acid-etched (SLActive) surface and with a Ti6Al4V alloy that was sand-blasted and acid-washed. Cylindrical implants with two, 0.75 mm deep, circumferential grooves were placed in the maxilla of miniature pigs and allowed to heal for 1, 2, 4 and 8 weeks. Undecalcified toluidine blue-stained ground sections were produced. Surface topography, area fraction of tissue components, and bone-to-implant contact (BIC) were determined. All materials showed significantly different surface roughness parameters. The amount of new bone within the implant grooves increased over time, without significant differences between materials. However, BIC values were significantly related to the implant material and the healing period. For TiZr and cpTi implants, the BIC increased over time, reaching values of 59.38 % and 76.15 % after 2 weeks, and 74.50 % and 84.67 % after 8 weeks, respectively. In contrast, the BIC for Ti6Al4V implants peaked with 42.29 % after 2 weeks followed by a decline to 28.60 % at 8 weeks. Significantly more surface was covered by multinucleated giant cells on Ti6Al4V implants after 4 and 8 weeks. In conclusion, TiZr and cpTi implants showed faster osseointegration than Ti6Al4V implants. Both chemistry and surface topography might have influenced the results. The use of diameter-reduced TiZr implants in more challenging clinical situations warrants further documentation in long-term clinical studies.

Zerbrochene Spiegel /1

Der Beitrag beschreibt eine doppelte, verfremdete und letztendlich tragische Spiegelung in der Wahrnehmung von Architektur zwischen Europa und Indien: zwischen 1780 und 1856 entstanden in der nordindischen Stadt Lucknow mehrere große Baukomplexe, die von den indisch-islamischen Herrschern der Stadt in europäisch-klassizistischen Formen gestaltet wurden. Nach dem indischen Aufstand, der in den Jahren 1857 und 1858 gegen die britische Herrschaft in Lucknow losbrach, wurden diese Bauten zum Gegenstand einer scharfen europäischen Architekturkritik. Der erste Abschnitt – "Das Eigene und das Fremde" – betrachtet die westliche Rezeption dieser europäisch-klassizistischen Bauten, die über Jahrzehnte durch ein Negativurteil bestimmt war, das sich aus der politischen Interpretation des indischen Aufstands erklärt. Der zweite Abschnitt – "Kopie und Synthese" – geht auf die Suche nach den Zusammenhängen für die positive Europarezeption in Lucknow und für die negative Kritik dieser Bauten in Europa. Es erweist sich, dass die Praxis von Architekturkopie und die Wahrnehmung europäischer Stilformen bei der Übernahme klassizistischer Motive in Indien deutlich anders war als das exakte und moralisch überhöhte Verständnis von Stilformen im Europa nach 1850.

Zerbrochene Spiegel /2

Der Beitrag beschreibt eine doppelte, verfremdete und letztendlich tragische Spiegelung in der Wahrnehmung von Architektur zwischen Europa und Indien: zwischen 1780 und 1856 entstanden in der nordindischen Stadt Lucknow mehre-re große Baukomplexe, die von den indisch-islamischen Herrschern der Stadt in europäisch-klassizistischen Formen gestaltet wurden. Nach dem indischen Auf-stand, der in den Jahren 1857 und 1858 gegen die britische Herrschaft in Lucknow losbrach, wurden diese Bauten zum Gegenstand einer scharfen europäi-scher Architekturkritik. Der erste Abschnitt – "Das Eigene und das Fremde" – betrachtet die westliche Rezeption dieser europäisch-klassizistischen Bauten, die über Jahrzehnte durch ein Negativurteil bestimmt war, das sich aus der politischen Interpretation des indischen Aufstands erklärt. Der zweite Abschnitt – "Kopie und Synthese" – geht auf die Suche nach den Zusammenhängen für die positive Europarezeption in Lucknow und für die negative Kritik dieser Bauten in Europa. Es erweist sich, dass die Praxis von Architekturkopie und die Wahrnehmung europäischer Stilfor-men bei der Übernahme klassizistischer Motive in Indien deutlich anders war als das exakte und moralisch überhöhte Verständnis von Stilformen im Europa nach 1850.

Falkland Island English

This chapter examines some of the grammatical variability and non-standardness found in the English of the Falkland Islands. The Falklands are an archipelago of over 700 islands located in the western South Atlantic Ocean, 480km off the east coast of Argentina. Although the population is small – around 3000 - the islands cover an area of over 12000km2 – slightly larger than Jamaica and half the size of Wales, making them, after Greenland, the most sparsely populated political entity in the world. In political terms, the Falklands are an Overseas Territory of the United Kingdom. In contrast to the rural isolated image that the Falklands perhaps conjure up, the community is, in demographic terms, an urban and diverse one. Over 85% of the population living in the capital Stanley. The 2006 census (Government of the Falkland Islands 2007: 6) shows that 55% of the population were not born on the Islands, with the largest migrant groups coming from the UK, St Helena (another British Overseas Territory, located in the eastern South Atlantic), Chile and Australia. It also highlighted the fact that people born in 62 different countries were resident on the islands at the time (Pascoe and Pepper 2008: 38). By way of a comparison, only Monaco and Andorra, in Europe, have a higher proportion of their populations made up of migrants. In addition to the local Falkland population, there is a large military presence on the islands at the Royal Airforce Base at Mount Pleasant, 50km south-west of Stanley. The Head of State is the monarch of the UK, who is represented on the islands by a governor. The democratically elected 11-member Legislative Assembly is responsible for day-to-day government of the islands. The Falklands are perhaps most famous because of their 74 day occupation by Argentina in 1982. It is not appropriate here to go into detail about the dispute between the UK and Argentina about the sovereignty of the Islands. What is undisputed is that there has been a continuous Anglophone speech community on the islands since the early 1830s, making it one of the most recently developed ‘Inner Circle’ (Kachru 1985) Englishes in the world. This chapter examines the grammatical characteristics of Falkland Island English, drawn from a transcribed corpus of over 500,000 words of informal conversational speech, collected by Andrea Sudbury both in Stanley and in ‘Camp’ (the local name for the rest of the islands) (see Sudbury 2000, 2001 for more details about the methods used in the survey).

CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture.

Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1β and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 co-immunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.

Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Una bella roba. ‘Novellare’ als Erzählkonzept in Boccaccios ›Decameron‹

Der narrative Entwurf von Boccaccios ›Decameron‹ und Boccaccios theoretische Reflexionen über das Erzählen stehen klar im Fluchtpunkt der horazischen Lehre des prodesse et delectare. Vor diesem Horizont entwickelt Boccaccio sein Konzept des novellare, das einerseits ein ‚Wiedererzählen’ (analog zu mhd. erniuwen) beinhaltet und andererseits zu einer neuen Autonomie des Erzählens vorstößt. Beobachten lässt sich dieser Vorgang des Erneuerns weniger in Boccaccios theoretischen Ausführungen (etwa im Schlusswort des ›Decameron‹ oder in den ›Genealogie deorum gentilium‹) als in seiner dichterischen Praxis. Als Schlüsseltext wird im Vortrag die Novelle von der duldsamen Griselda herangezogen, die das ›Decameron‹ beschließt und die mit den Worten una bella roba endet. Das ‚schöne Kleid’ ist einerseits traditionelle Dichtungsmetapher (im Horizont des investire bzw. integumentum), andererseits intradiegetischer Bestandteil des Erzähl-‚Stoffs’ der Novelle. Bei Boccaccio dürfte das Gewand der Griselda, zusammen mit deren wiederholt thematisierter Nacktheit, dazu dienen, eine in die Novelle verpackte stoische Lehre zu vergegenwärtigen, diese in eine Erzählung ‚einzukleiden’. Das Kleid der Griselda wird so zur ‚Pathosformel’ (in der Begrifflichkeit A. Warburgs) bzw. zum ‚Faltenwurf’ (in der Begrifflichkeit G. Didi-Hubermans), mithin zur Verkörperung eines ‚neuen Erzählens’, das sich (im Gegensatz etwa zu Dante) von metaphysischen Entwürfen emanzipiert und in der Autonomie sprachlicher Kunstfertigkeit, bis an die Grenzen des Erzählbaren gehend und didaktische Ansprüche überwindend, die Möglichkeiten literarischer Darstellung ausreizt. Von den Zeitgenossen wurde dieses Experiment zwar wahrgenommen, in seinen Dimensionen aber nur ansatzweise erkannt. Symptomatisch für diese Form der Rezeption ist Petrarcas lateinische Übersetzung der ›Griselda‹-Novelle (›Seniles‹, XVII,3), wobei der Verfasser – seinerseits die Kleidermetaphorik bemühend – das Übersetzen als ein stilo alio retexere auffasst und seine Version den (wohl vorwiegend männlich intendierten Lesern) als auf Gott hin orientierte Lehre anempfiehlt: ut legentes ad imitandam saltem femine constantiam excitarem, ut [...] hoc prestare Deo nostro audeant. Diese Rückführung von Boccaccios erzählerischem Wagnis ins Didaktische zeigt sich auch in der Rezeption von Petrarcas Übersetzung, durch welche die Novelle im Europa des 14. und 15. Jahrhunderts weite Verbreitung fand: In einer der Haupthandschriften von Chaucers ›Canterbury Tales‹, dem Hengwrt Manuscript (Aberystwyth, National Library of Wales), wird die auf der ›Griselda‹-Novelle aufbauende Erzählung des Scholaren (›The Clerk’s Tale‹) mit Bestandteilen aus Petrarcas Übersetzung glossiert; in einer Handschrift aus dem Besitz des Nürnberger Humanisten Hartmann Schedel (München, Bayerische Staatsbibliothek, Clm 504) wird Petrarcas Konzept des stilo alio retexere erläutert als: claram facere, nudare [...], aperire, wobei hier die in Boccaccios Novelle intradiegetisch enthaltene Spannung von ‚Einkleidung’ und ‚Nacktheit’ auf einer lehrhaften Ebene fortwirkt.