Listening in to others : in between noise and silence

Since the launch of the ‘Clean Delhi, Green Delhi’ campaign in 2003, slums have become a significant social and political issue in India’s capital city. Through this campaign, the state, in collaboration with Delhi’s middle class through the ‘Bhagidari system’ (literally translated as ‘participatory system’), aims to transform Delhi into a ‘world-class city’ that offers a sanitised, aesthetically appealing urban experience to its citizens and Western visitors. In 2007, Delhi won the bid to host the 2010 Commonwealth Games; since then, this agenda has acquired an urgent, almost violent, impetus to transform Delhi into an environmentally friendly, aesthetically appealing and ‘truly international city’. Slums and slum-dwellers, with their ‘filth, dirt, and noise’, have no place in this imagined city. The violence inflicted upon slum-dwellers, including the denial of their judicial rights, is justified on these accounts. In addition, the juridical discourse since 2000 has ‘re-problematised slums as ‘nuisance’. The rising antagonism of the middle-classes against the poor, supported by the state’s ambition to have a ‘world-class city’, has allowed a new rhetoric to situate the slums in the city. These representations articulate slums as homogenised spaces of experience and identity. The ‘illegal’ status of slum-dwellers, as encroachers upon public space, is stretched to involve ‘social, cultural, and moral’ decadence and depravity. This thesis is an ethnographic exploration of everyday life in a prominent slum settlement in Delhi. It sensually examines the social, cultural and political materiality of slums, and the relationship of slums with the middle class. In doing so, it highlights the politics of sensorial ordering of slums as ‘filthy, dirty, and noisy’ by the middle classes to calcify their position as ‘others’ in order to further segregate, exclude and discriminate the slums. The ethnographic experience in the slums, however, highlights a complex sensorial ordering and politics of its own. Not only are the interactions between diverse communities in slums highly restricted and sensually ordained, but the middle class is identified as a sensual ‘other’, and its sensual practices prohibited. This is significant in two ways. First, it highlights the multiplicity of social, cultural experience and engagement in the slums, thereby challenging its homogenised representation. Second, the ethnographic exploration allowed me to frame a distinct sense of self amongst the slums, which is denied in mainstream discourses, and allowed me to identify the slums’ own ’others’, middle class being one of them. This thesis highlights sound – its production, performances and articulations – as an act with social, cultural, and political implications and manifestations. ‘Noise’ can be understood as a political construct to identify ‘others’ – and both slum-dwellers and the middle classes identify different sonic practices as noise to situate the ‘other’ sonically. It is within this context that this thesis frames the position of Listener and Hearer, which corresponds to their social-political positions. These positions can be, and are, resisted and circumvented through sonic practices. For instance, amplification tactics in the Karimnagar slums, which are understood as ‘uncultured, callous activities to just create more noise’ by the slums’ middle-class neighbours, also serve definite purposes in shaping and navigating the space through the slums’ soundscapes, asserting a presence that is otherwise denied. Such tactics allow the residents to define their sonic territories and scope of sonic performances; they are significant in terms of exerting one’s position, territory and identity, and they are very important in subverting hierarchies. The residents of the Karimnagar slums have to negotiate many social, cultural, moral and political prejudices in their everyday lives. Their identity is constantly under scrutiny and threat. However, the sonic cultures and practices in the Karimnagar slums allow their residents to exert a definite sonic presence – which the middle class has to hear. The articulation of noise and silence is an act manifesting, referencing and resisting social, cultural, and political power and hierarchies.

Cell sourcing for bone tissue engineering : amniotic fluid stem cells have a delayed, robust differentiation compared to mesenchymal stem cells

Cell based therapies for bone regeneration are an exciting emerging technology, but the availability of osteogenic cells is limited and an ideal cell source has not been identified. Amniotic fluid-derived stem (AFS) cells and bone-marrow derived mesenchymal stem cells (MSCs) were compared to determine their osteogenic differentiation capacity in both 2D and 3D environments. In 2D culture, the AFS cells produced more mineralized matrix but delayed peaks in osteogenic markers. Cells were also cultured on 3D scaffolds constructed of poly-e-caprolactone for 15 weeks. MSCs differentiated more quickly than AFS cells on 3D scaffolds, but mineralized matrix production slowed considerably after 5 weeks. In contrast, the rate of AFS cell mineralization continued to increase out to 15 weeks, at which time AFS constructs contained 5-fold more mineralized matrix than MSC constructs. Therefore, cell source should be taken into consideration when used for cell therapy, as the MSCs would be a good choice for immediate matrix production, but the AFS cells would continue robust mineralization for an extended period of time. This study demonstrates that stem cell source can dramatically influence the magnitude and rate of osteogenic differentiation in vitro.

Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Mesoporous bioglass/silk composite scaffolds for bone tissue engineering

In the past 20 years, mesoporous materials have been attracted great attention due to their significant feature of large surface area, ordered mesoporous structure, tunable pore size and volume, and well-defined surface property. They have many potential applications, such as catalysis, adsorption/separation, biomedicine, etc. [1]. Recently, the studies of the applications of mesoporous materials have been expanded into the field of biomaterials science. A new class of bioactive glass, referred to as mesoporous bioactive glass (MBG), was first developed in 2004. This material has a highly ordered mesopore channel structure with a pore size ranging from 5–20 nm [1]. Compared to non-mesopore bioactive glass (BG), MBG possesses a more optimal surface area, pore volume and improved in vitro apatite mineralization in simulated body fluids [1,2]. Vallet-Regí et al. has systematically investigated the in vitro apatite formation of different types of mesoporous materials, and they demonstrated that an apatite-like layer can be formed on the surfaces of Mobil Composition of Matters (MCM)-48, hexagonal mesoporous silica (SBA-15), phosphorous-doped MCM-41, bioglass-containing MCM-41 and ordered mesoporous MBG, allowing their use in biomedical engineering for tissue regeneration [2-4]. Chang et al. has found that MBG particles can be used for a bioactive drug-delivery system [5,6]. Our study has shown that MBG powders, when incorporated into a poly (lactide-co-glycolide) (PLGA) film, significantly enhance the apatite-mineralization ability and cell response of PLGA films. compared to BG [7]. These studies suggest that MBG is a very promising bioactive material with respect to bone regeneration. It is known that for bone defect repair, tissue engineering represents an optional method by creating three-dimensional (3D) porous scaffolds which will have more advantages than powders or granules as 3D scaffolds will provide an interconnected macroporous network to allow cell migration, nutrient delivery, bone ingrowth, and eventually vascularization [8]. For this reason, we try to apply MBG for bone tissue engineering by developing MBG scaffolds. However, one of the main disadvantages of MBG scaffolds is their low mechanical strength and high brittleness; the other issue is that they have very quick degradation, which leads to an unstable surface for bone cell growth limiting their applications. Silk fibroin, as a new family of native biomaterials, has been widely studied for bone and cartilage repair applications in the form of pure silk or its composite scaffolds [9-14]. Compared to traditional synthetic polymer materials, such as PLGA and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), the chief advantage of silk fibroin is its water-soluble nature, which eliminates the need for organic solvents, that tend to be highly cytotoxic in the process of scaffold preparation [15]. Other advantages of silk scaffolds are their excellent mechanical properties, controllable biodegradability and cytocompatibility [15-17]. However, for the purposes of bone tissue engineering, the osteoconductivity of pure silk scaffolds is suboptimal. It is expected that combining MBG with silk to produce MBG/silk composite scaffolds would greatly improve their physiochemical and osteogenic properties for bone tissue engineering application. Therefore, in this chapter, we will introduce the research development of MBG/silk scaffolds for bone tissue engineering.

Limitations and challenges in MSC delivery for bone regeneration

Objective: Regeneration of osseous defects by tissue-engineering or cell delivery approach provides a novel means of treatment utilizing cell biology, materials sciences, and molecular biology. The concept of in vitro explanted mesenchymal stem cells (MSCs) with an ability to induce new bone formation has been demonstrated in some small animal models. However, contradictory results have been reported regarding the regenerative capacity of MSCs after ex vivo expansion due to the lack of the understanding of microenvironment for MSC differentiation in vivo. ----- ----- Methods: In our laboratory tissue-derived and bone marrow-derived MSCs have been investigated in their osteogenesis. Cell morphology and proliferation were studied by microscopy, confocal microscopy, FACS and cell counting. Cell differentiation and matrix formation were analysed by matrix staining, quantitative PCR, and immunohistochemistry. A SCID skull defect model was used for cell transplantation studies.----- ----- Results: It was noted that tissue-derived and bone marrow-derived MSCs showed similar characteristics in cell surface marker expression, mesenchymal lineage differentiation potential, and cell population doubling. MSCs from both sources could initiate new bone formation in bone defects after delivery into a critical size defects. The bone forming cells were from both transplanted cells and endogenous cells from the host. Interestingly, the majority of in vitro osteogenic differentiated cells did not form new bone directly even though mineralized matrix was synthesized in vitro by MSCs. Furthermore, no new bone formation was detected when MSCs were transplanted subcutaneously.----- ----- Conclusion: This study unveiled the limitations of MSC delivery in bone regeneration and proposed that in vivo microenvironment needs to be optimized for MSC delivery in osteogenesis.

Mechanical Behavior of Articular Cartilage After Osteochondral Autograft Transfer in an Ovine Model

BACKGROUND: Grafting of autologous hyaline cartilage and bone for articular cartilage repair is a well-accepted technique. Although encouraging midterm clinical results have been reported, no information on the mechanical competence of the transplanted joint surface is available. HYPOTHESIS: The mechanical competence of osteochondral autografts is maintained after transplantation. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral defects were filled with autografts (7.45 mm in diameter) in one femoral condyle in 12 mature sheep. The ipsilateral femoral condyle served as the donor site, and the resulting defect (8.3 mm in diameter) was left empty. The repair response was examined after 3 and 6 months with mechanical and histologic assessment and histomorphometric techniques. RESULTS: Good surface congruity and plug placement was achieved. The Young modulus of the grafted cartilage significantly dropped to 57.5% of healthy tissue after 3 months (P < .05) but then recovered to 82.2% after 6 months. The aggregate and dynamic moduli behaved similarly. The graft edges showed fibrillation and, in some cases (4 of 6), hypercellularity and chondrocyte clustering. Subchondral bone sclerosis was observed in 8 of 12 cases, and the amount of mineralized bone in the graft area increased from 40% to 61%. CONCLUSIONS: The mechanical quality of transplanted cartilage varies considerably over a short period of time, potentially reflecting both degenerative and regenerative processes, while histologically signs of both cartilage and bone degeneration occur. CLINICAL RELEVANCE: Both the mechanically degenerative and restorative processes illustrate the complex progression of regeneration after osteochondral transplantation. The histologic evidence raises doubts as to the long-term durability of the osteochondral repair.

Strategy in developing cell based therapy for large bone

Regeneration of osseous defects by tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. The concept of in vitro cultured osteoblasts having an ability to induce new bone formation has been demonstrated in the critical size defects using small animal models. The bone derived cells can be incorporated into bioengineered scaffolds and synthesize bone matrix, which on implantation can induce new bone formation. In search of optimal cell delivery materials, the extracellular matrix as cell carriers for the repair and regeneration of tissues is receiving increased attention. We have investigated extracellular matrix formed by osteoblasts in vitro as a scaffold for osteoblasts transplantation and found a mineralized matrix, formed by human osteoblasts in vitro, can initiate bone formation by activating endogenous mesenchymal cells. To repair the large bone defects, osteogenic or stem cells need to be prefabricated in a large three dimensional scaffold usually made of synthetic biomaterials, which have inadequate interaction with cells and lead to in vivo foreign body reactions. The interstitial extracellular matrix has been applied to modify biomaterials surface and identified vitronectin, which binds the heparin domain and RGD (Arg-Gly-Asp) sequence can modulate cell spreading, migration and matrix formation on biomaterials. We also synthesized a tri-block copolymer, methoxy-terminated poly(ethylene glycol)(MPEG)-polyL-lactide(PLLA)-polylysine(PLL) for human osteoblasts delivery. We identified osteogenic activity can be regulated by the molecular weight and composition of the triblock copolymers. Due to the sequential loss of lineage differentiation potential during the culture of bone marrow stromal cells that hinderers their potential clinical application, we have developed a clonal culture system and established several stem cell clones with fast growing and multi-differentiation properties. Using proteomics and subtractive immunization, several differential proteins have been identified and verified their potential application in stem cell characterization and tissue regeneration

The effects of pore architecture in silk fibroin scaffolds on the growth and differentiation of BMP7-expressing mesenchymal stem cells

Pore architecture of scaffolds is known to play a critical role in tissue engineering as it provides the vital framework for the seeded cells to organize into a functioning tissue. In this report, we investigated the effects of different concentration on silk fibroin protein 3D scaffold pore microstructure. Four pore size ranges of silk fibroin scaffolds were made by freeze-dry technique, with the pore sizes ranging from 50 to 300 µm. The pore size of the scaffold decreases as the concentration increases. Human mesenchymal stem cells were in vitro cultured in these scaffolds. After BMP7 gene transferred, DNA assay, ALP assay, hematoxylin–eosin staining, alizarin red staining and reverse transcription-polymerase chain reaction were performed to analyze the effect of the pore size on cell growth, differentiation and the secretion of extracellular matrix (ECM). Cell morphology in these 3D scaffolds was investigated by confocal microscopy. This study indicates mesenchymal stem cells prefer the group of scaffolds with pore size between 100 and 300 µm for better proliferation and ECM production

CaSiO3 microstructure modulating the in vitro and in vivo bioactivity of poly (lactide-co-glycolide) microspheres

Poly (lactide-co-glycolide) (PLGA) microspheres have been used for regenerative medicine due to their ability for drug delivery and generally good biocompatibility, but they lack adequate bioactivity for bone repair application. CaSiO3 (CS) has been proposed as a new class of material suitable for bone tissue repair due to its excellent bioactivity. In this study, we set out to incorporate CS into PLGA microspheres to investigate how the phase structure (amorphous and crystal) of CS influences the in vitro and in vivo bioactivity of the composite microspheres, with a view to the application for bone regeneration. X-ray diffraction (XRD), N2 adsorption-desorption analysis and scanning electron microscopy (SEM) were used to analyze the phase structure, surface area/pore volume, and microstructure of amorphous CS (aCS) and crystal CS (cCS), as well as their composite microspheres. The in vitro bioactivity of aCS and cCS – PLGA microspheres was evaluated by investigating their apatite-mineralization ability in simulated body fluids (SBF) and the viability of human bone mesenchymal stem cells (BMSCs). The in vivo bioactivity was investigated by measuring their de novo bone-formation ability. The results showed that the incorporation of both aCS and cCS enhanced the in vitro and in vivo bioactivity of PLGA microspheres. cCS/PLGA microspheres improved better in vitro BMSC viability and de novo bone-formation ability in vivo, compared to aCS/PLGA microspheres. Our study indicates that controlling the phase structure of CS is a promising method to modulate the bioactivity of polymer microsphere system for potential bone tissue regeneration.

Preclinical animal models for segmental bone defect research and tissue engineering

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. Analysing the tissue engineering literature it can be concluded that bone regeneration has become a focus area in the field. Hence, a considerable number of research groups and commercial entities work on the development of tissue engineered constructs for bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. In translational orthopaedic research, the utilisation of large preclinical animal models is a conditio sine qua non. Consequently, to allow comparison between different studies and their outcomes, it is essential that animal models, fixation devices, surgical procedures and methods of taking measurements are well standardized to produce reliable data pools as a base for further research directions. The following chapter reviews animal models of the weight-bearing lower extremity utilized in the field which include representations of fracture-healing, segmental bone defects, and fracture non-unions.

Early osteogenic response of osteoprogenitor cells on modified titanium implant surfaces leads to improved osteogenesis

Background: Implant surface micro-roughness and hydrophilicity are known to improve the osteogenic differentiation potential of osteoprogenitor cells. This study was aimed to determine whether topographically and chemically modified titanium implant surfaces stimulate an initial osteogenic response in osteoprogenitor cells, which leads to their improved osteogenesis. ----- ----- Methods: Statistical analysis of microarray gene expression profiling data available from studies (at 72 hours) on sand-blasted, large grit acid etched (SLA) titanium surfaces was performed. Subsequently, human osteoprogenitor cells were cultured on SLActive (hydrophilic SLA), SLA and polished titanium surfaces for 24 hours, 3 days and 7 days. The expression of BMP2, BMP6, BMP2K, SP1, ACVR1, FZD6, WNT5A, PDLIM7, ITGB1, ITGA2, OCN, OPN, ALP and RUNX2 were studied using qPCR. ----- ----- Results: Several functional clusters related to osteogenesis were highlighted when genes showing statistically significant differences (from microarray data at 72 hours) in expression on SLA surface (compared with control surface) were analysed using DAVID (online tool). This indicates that differentiation begins very early in response to modified titanium surfaces. At 24 hours, ACVR1 (BMP pathway), FZD6 (Wnt pathway) and SP1 (TGF-β pathway) were significantly up-regulated in cultures on the SLActive surface compared to the other surfaces. WNT5A and ITGB1 also showed higher expression on the modified surfaces. Gene expression patterns on Day 3 and Day 7 did not reveal any significant differences.----- ----- Conclusion: These results suggest that the initial molecular response of osteoprogenitor cells to modified titanium surfaces may be responsible for an improved osteogenic response via the BMP and Wnt signalling pathways.

Design for eco-services. Part A - Environmental Services

Without the virtually free services of nature like clean air and water, humans would not last long. Natural systems can be incorporated in existing urban structures or spaces to add public amenity, mitigate the heat island effect, reduce pollution, add oxygen, and ensure water, electricity and food security in urban areas. Th ere are many eco-solutions that could radically reduce resource consumption and pollution and even provide surplus ecosystem services in the built environment at little or no operational cost, if adequately supported by design. Th is paper is the fi rst of a two part paper that explains what eco-services are, then provides examples of how design can generate natural as well as social capital. Using examples of actual and notional solutions, both papers set out to challenge designers to ‘think again’, and invent ways of creating net positive environmental gains through built environment design.

Design for eco-services. Part B - Building Services

Without the virtually free services of nature like clean air and water, humans would not last long. Natural systems can be incorporated in existing urban structures or spaces to add public amenity, mitigate the heat island eff ect, reduce pollution, add oxygen, and ensure water, electricity and food security in urban areas. Th ere are many eco-solutions that could radically reduce resource consumption and pollution and even provide surplus ecosystem services in the built environment at little or no operational cost, if adequately supported by design. Th is is the second part of a two part paper that explains what eco-services are, then provides examples of how design can generate natural as well as social capital. Using examples of actual and notional solutions, both papers set out to challenge designers to ‘think again’, and invent ways of creating net positive environmental gains through built environment design.

Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells

In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.