Effect of bone graft type on fusion rates following endoscopic anterior scoliosis correction

Bone graft is generally considered fundamental in achieving solid fusion in scoliosis correction and pseudarthrosis following instrumentation may predispose to implant failure. In endoscopic anterior-instrumented scoliosis surgery, autologous rib or iliac crest graft has been utilised traditionally but both techniques increase operative duration and cause donor site morbidity. Allograft bone and bone- morphogenetic-protein alternatives may improve fusion rates but this remains controversial. This study's objective was to compare two-year postoperative fusion rates in a series of patients who underwent endoscopic anterior instrumentation for thoracic scoliosis utilising various bone graft types. Significantly better rates of fusion occurred in endoscopic anterior instrumented scoliosis correction using femoral allograft compared to autologous rib-heads and iliac crest graft. This may be partly explained by the difficulty obtaining sufficient quantities of autologous graft. Lower fusion rates in the autologous graft group appeared to predispose to rod fracture although the clinical consequence of implant failure is uncertain.

Implication of 3D culture system for study of prostate cancer (CaP) mediated bone metastasis

Introduction : For the past decade, three dimensional (3D) culture has served as a foundation for regenerative medicine study. With an increasing awareness of the importance of cell-cell and cell-extracellular matrix interactions which are lacking in 2D culture system, 3D culture system has been employed for many other applications namely cancer research. Through development of various biomaterials and utilization of tissue engineering technology, many in vivo physiological responses are now better understood. The cellular and molecular communication of cancer cells and their microenvironment, for instance can be studied in vitro in 3D culture system without relying on animal models alone. Predilection of prostate cancer (CaP) to bone remains obscure due to the complexity of the mechanisms and lack of proper model for the studies. In this study, we aim to investigate the interaction between CaP cells and osteoblasts simulating the natural bone metastasis. We also further investigate the invasiveness of CaP cells and response of androgen sensitve CaP cells, LNCaP to synthetic androgen.----- Method : Human osteoblast (hOB) scaffolds were prepared by seeding hOB on medical grade polycaprolactone-tricalcium phosphate (mPLC-TCP) scaffolds and induced to produce bone matrix. CaP cell lines namely wild type PC3 (PC3-N), overexpressed prostate specific antigen PC3 (PC3k3s5) and LNCaP were seeded on hOB scaffolds as co-cultures. Morphology of cells was examined by Phalloidin-DAPI and SEM imaging. Gelatin zymography was performed on the 48 hours conditioned media (CM) from co-cultures to determine matrix metalloproteinase (MMP) activity. Gene expression of hOB/LNCaP co-cultures which were treated for 48 hours with 1nM synthetic androgen R1881 were analysed by quantitative real time PCR (qRT-PCR).----- Results : Co-culture of PCC/hOB revealed that the morphology of PCCs on the tissue engineered bone matrix varied from homogenous to heterogenous clusters. Enzymatically inactive pro-MMP2 was detected in CM from hOBs and PCCs cultured on scaffolds. Elevation in MMP9 activity was found only in hOB/PC3N co-culture. hOB/LNCaP co-culture showed increase in expression of key enzymes associated with steroid production which also corresponded to an increase in prostate specific antigen (PSA) and MMP9.----- Conclusions : Upregulation of MMP9 indicates involvement of ECM degradation during cancer invasion and bone metastases. Expression of enzymes involved in CaP progression, PSA, which is not expressed in osteoblasts, demonstrates that crosstalk between PCCs and osteoblasts may play a part in the aggressiveness of CaP. The presence of steroidogenic enzymes, particularly, RDH5, in osteoblasts and stimulated expression in co-culture, may indicate osteoblast production of potent androgens, fuelling cancer cell proliferation. Based on these results, this practical 3D culture system may provide greater understanding into CaP mediated bone metastasis. This allows the role of the CaP/hOB interaction with regards to invasive property and steroidogenesis to be further explored.

Asset specificity and behavioural uncertainty as moderators of the sales growth : employment growth relationship in emerging ventures

Sales growth and employment growth are the two most widely used growth indicators for new ventures; yet, sales growth and employment growth are not interchangeable measures of new venture growth. Rather, they are related, but somewhat independent constructs that respond differently to a variety of criteria. Most of the literature treats this as a methodological technicality. However, sales growth with or without accompanying employment growth has very different implications for managers and policy makers. A better understanding of what drives these different growth metrics has the potential to lead to better decision making. To improve that understanding we apply transaction cost economics reasoning to predict when sales growth will be or will not be accompanied by employment growth. Our results indicate that our predictions are borne out consistently in resource-constrained contexts but not in resource-munificent contexts.

A review of models of spatial innovation infrastructures in support of high growth SMEs

This Paper first provides a review and analysis of the recent trends on innovation infrastructures developed in industrialised countries to promote innovation and competitiveness for high growth SMEs. It specifically aims to examine various spatial models developed to support provision of innovation infrastructure for high growth sector.

Entrepreneurship and family firms : a case study in growth and survival

Entrepreneurial marketing has gained popularity in both the entrepreneurship and marketing disciplines in recent times. The success of ventures that have pursued what are considered non-traditional marketing approaches has been attributed to entrepreneurial marketing practices. Despite the multitude of marketing concepts and models, there are prominent venture successes that do not conform to these and have thus been put in the ''entrepreneurial'' box. One only has to look to the ''Virgin'' model to put this in context. Branson has proven for example that not ''sticking to the knitting'' can work with the ways the Virgin portfolio has been diversified. Consequently, an entrepreneurial orientation is considered a desirable philosophy and has become prominent in such industries as airlines and information technology. Miles and Arnold (1991) found that entrepreneurial orientation is positively correlated to marketing orientation. They propose that entrepreneurial orientation is a strategic response by firms to turbulence in the environment. While many marketing successes are analysed in hindsight using traditional marketing concepts and strategies, there are those that challenge standard marketing textbook recommendations. Marketing strategy is often viewed as a process of targeting, segmenting and positioning (STP). Academics and consultants advocate this approach along with the marketing and business plans. The reality however is that a number of businesses do not practice these and pursue alternative approaches. Other schools of thought and business models have been developing to explain differences in orientation such as branding (Keller 2001), the service-dominant logic (Vargo and Lusch 2004) and effectuation logic (Sarasvathy 2001). This indicates that scholars are now looking to cognate fields to explain a given phenomenon beyond their own disciplines. Bucking this trend is a growing number of researchers working at the interface between entrepreneurship and marketing. There is now an emerging body of work dedicated to this interface, hence the development of entrepreneurial marketing as an alternative to the traditional approaches. Hills and Hultman (2008:3) define entrepreneurial marketing as ''a spirit, an orientation as well as a process of passionately pursuing opportunities and launching and growing ventures that create perceived customer value through relationships by employing innovativeness, creativity, selling, market immersion, networking and flexibility.'' Although it started as a special interest group, entrepreneurial marketing is now gaining recognition in mainstream entrepreneurship and marketing literature. For example new marketing textbooks now incorporate an entrepreneurial marketing focus (Grewal and Levy 2008). The purpose of this paper is to explore what entrepreneurial approaches are used by entrepreneurs and their impact on the success of marketing activities. Methodology/Key Propositions In order to investigate this, we employ two cases: 42Below, vodka producers from New Zealand and Penderyn Distillery, whisky distillers from Wales. The cases were chosen based on the following criteria. Firstly, both companies originate from small economies. Secondly, both make products (spirits) from locations that are not traditionally regarded as producers of their flagship products and thirdly, the two companies are different from each other in terms of their age. Penderyn is an old company established in 1882, whereas 42Below was founded only in 1999. Vodka has never been associated with New Zealand. By the same token, whisky has always been associated with Scotland and Ireland but never been with Wales. Both companies defied traditional stereotypes in marketing their flagship products and found international success. Using a comparative a case study approach, we use Covin and Slevin's (1989) set of items that purport to measure entrepreneurial orientation and apply a qualitative lens on the approaches of both companies. These are: 1. cultural emphases on innovation and R&D 2. high rate of new product introduction 3. bold, innovative product development 4. initiator proactive posture 5. first to introduce new technologies and products 6. competitive posture toward competitor 7. strong prolictivity for high risk, high return projects 8. environment requires boldness to achieve objectives 9. when faced with risk, adopts aggressive, bold posture. Results and Implications We find that both companies have employed entrepreneurial marketing approaches but with different intensities. While acknowledging that they are different from the norm, the specifics of their individual approaches are dissimilar. Both companies have positioned their products at the premium end of their product categories and have emphasised quality and awards in their communication strategies. 42Below has carved an image of irreverence and being non-conformist. They have unashamedly utilised viral marketing and entered international markets by training bartenders and hosting unconventional events. They use edgy language such as vodka university, vodka professors and vodka ambassadors. Penderyn Distillery has taken a more traditional approach to marketing its products and portraying romantic images of age-old tradition of distilling as key to their positioning. Both companies enjoy success as evidenced by industry awards and international acclaim.

Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo

The use of polycaprolactone (PCL) as a biomaterial, especially in the fields of drug delivery and tissue engineering, has enjoyed significant growth. Understanding how such a device or scaffold eventually degrades in vivo is paramount as the defect site regenerates and remodels. Degradation studies of three-dimensional PCL and PCL-based composite scaffolds were conducted in vitro (in phosphate buffered saline) and in vivo (rabbit model). Results up to 6 months are reported. All samples recorded virtually no molecular weight changes after 6 months, with a maximum mass loss of only about 7% from the PCL-composite scaffolds degraded in vivo, and a minimum of 1% from PCL scaffolds. Overall, crystallinity increased slightly because of the effects of polymer recrystallization. This was also a contributory factor for the observed stiffness increment in some of the samples, while only the PCL-composite scaffold registered a decrease. Histological examination of the in vivo samples revealed good biocompatibility, with no adverse host tissue reactions up to 6 months. Preliminary results of medical-grade PCL scaffolds, which were implanted for 2 years in a critical-sized rabbit calvarial defect site, are also reported here and support our scaffold design goal for gradual and late molecular weight decreases combined with excellent long-term biocompatibility and bone regeneration. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 90A: 906-919, 2009

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2-4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae. In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalised bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity). Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4-5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.

The effect of bone graft type on fusion rates following anterior thoracoscopic scoliosis correction

Bone graft is generally considered fundamental in achieving solid fusion in scoliosis correction and pseudarthrosis following instrumentation may predispose to implant failure. In thoracoscopic anterior-instrumented scoliosis surgery, autologous rib or iliac crest graft has been utilised traditionally but both techniques increase operative duration and cause donor site morbidity. Allograft bone and bone morphogenetic protein (BMP) alternatives may improve fusion rates but this remains controversial. This study's objective was to compare two-year postoperative fusion rates in a series of patients who underwent thoracoscopic anterior instrumentation for thoracic scoliosis utilising various bone graft types.

Reduction of Secondary Degeneration after Spinal Cord Injury by Acute Delivery of Proinflammatory Growth Factors

INTRODUCTION Inflammation is a protective attempt to facilitate the removal of damaged tissue and to initiate the healing response in other tissues. However, after spinal cord injury (SCI), this response is prolonged leading to secondary degeneration and glial scarring. Here, we investigate the potential of sustained delivery of pro-inflammatory factors vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) to increase early inflammatory events and promote inflammatory resolution. Method Animal ethics approval was obtained from the Queensland University of Technology. Adult Wistar-Kyoto rats (12-16 weeks old) were subjected to laminectomies and T10 hemisections. Animals were then randomised to treatment (implantation of osmotic pump (Alzet) loaded with 5ug VEGF & 5 ug PDGF) or control groups (lesion control or lesion plus pump delivering PBS). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200(NF200) and anti- ionized calcium binding adapter molecule 1 (Iba1). One way ANOVA was used for statistic analysis. Results At 1 month, active pump-treated cords showed a high level of axonal filament throughout the defects as compared to the control groups. The mean lesion size, as measured by NF200, was 0.47mm2 for the lesion control, 0.39mm2 for the vehicle control and 0.078mm2 for the active pump group. Significant differences were detected between the active pump group and the two control groups (AP vs LC p= 0.017 AG vs VC p= 0.004). Iba-1 staining also showed significant differences in the post-injury inflammatory response. Discussion We have shown that axons and activated microglia are co-located in the lesion of the treated cord. We hypothesise the delivery of VEGF/PDGF increases the local vessel permeability to inflammatory cells and activates these along with the resident microglia to threshold population, which ultimately resolved the prolonged inflammation. Here, we have shown that maintaining the inflammatory signals for at least 7 days improved the morphology of the injured cord. Conclusion This study has shown that boosting inflammation, by delivery VEGF/PDGF, in the early phase of SCI helps to reduce secondary degeneration and may promote inflammation resolution. This treatment may provide a platform for other neuro-regenrative therapies.

The big brother : monitoring urban growth and change for sustainable infrastructure provision

Monitoring urban growth and land-use change is an important issue for sustainable infrastructure planning. Rapid urban development, sprawl and increasing population pressure, particularly in developing nations, are resulting in deterioration of infrastructure facilities, loss of productive agricultural lands and open spaces, pollution, health hazards and micro-climatic changes. In addressing these issues effectively, it is crucial to collect up-to-date and accurate data and monitor the changing environment at regular intervals. This chapter discusses the role of geospatial technologies for mapping and monitoring the changing environment and urban structure, where such technologies are highly useful for sustainable infrastructure planning and provision.

Cyclic strain disrupts endothelial network formation on Matrigel

Most forms of tissue healing depend critically on revascularisation. In soft tissues and in vitro, mechanical stimuli have been shown to promote vessel-forming activity. However, in bone defects, increased interfragmentary motion impairs vascular regeneration. Because these effects seem contradictory, we aimed to determine whether a range of mechanical stimuli exists in which angiogenesis is favoured. A series of cyclic strain magnitudes were applied to a Matrigel-based “tube formation” assay and the total lengths of networks formed by human microvascular endothelial cells measured at 24 h. Network lengths were reduced at all strain levels, compared to unstretched controls. However, the levels of pro-angiogenic matrix metalloproteases-2 and -9 in the corresponding conditioned media were unchanged by strain, and vascular endothelial growth factor was uniformly elevated in stretched conditions. By repeating the assay with the addition of conditioned media from mesenchymal stem cells cultivated in similar conditions, paracrine stimuli were shown to increase network lengths, but not to alter the negative effect of cyclic stretching. Together, these results demonstrate that directly applied periodic strains can inhibit endothelial organisation in vitro, and suggest that this may be due to physical disruption rather than biochemical modulation. Most importantly, the results indicate that the straining of endothelial cells and their assembly into vascular-like structures must be studied simultaneously to adequately characterise the mechanical influence on vessel formation.

Ceramic membranes for separation of proteins and DNA by in situ growth of alumina nanofibres with a nanomesh of metal oxide nanofibres

Ceramic membranes were fabricated by in situ synthesis of alumina nanofibres in the pores of an alumina support as a separation layer, and exhibited a high permeation selectivity for bovine serum albumin relative to bovine hemoglobin (over 60 times) and can effectively retain DNA molecules at high fluxes.

Organic and acquisitive employment growth : re-examining,testing and extending Penrose's Growth Theory.

Edith Penrose’s theory of firm growth postulates that a firm’s current growth rate will be influenced by the adjustment costs of, and changes to a firm’s productive opportunity set arising from, previous growth. Although she explicitly considered the impact of previous organic growth on current organic growth, she was largely silent about the impact of previous acquisitive growth. In this paper we extend Penrose’s work to examine that the relative impact of organic and acquisitive growth on the adjustment costs and productive opportunity set of the firm. Employing a panel of commercially active enterprises in Sweden over a 10 year period our results suggest the following. First, previous organic growth acts as a constraint on current organic growth. Second, previous acquisitive growth has a positive effect on current organic growth. We conclude that organic growth and acquisitive growth constitute two distinct strategic options facing the firm, which have a differential impact on the future organic growth of the firm.

The role of periosteum : a neglected aspect of osteoporosis

Most current studies on the pathogenesis of osteoporosis emphasize the bone metabolic activities occurring on endosteal surfaces, whereas the periosteal aspect is somewhat neglected. In terms of bone physiology, periosteum plays a determining role in de novo cortical bone formation and cortical bone expansion through periosteum is the most efficient way of increasing bone strength against fractures. Despite the important role of periosteum in the pathogenesis and treatment of osteoporosis, little is known about the structural and cellular features of periosteum in osteoporosis. This chapter will focus on the major changes occurring in the periosteum of osteoporosis and possible implications of these changes in the pathogenesis of osteoporosis. The changes identified in the periosteum of osteoporosis are mainly located in the metaphyseal compartment, which include: (a) much thicker and more cellular cambial layer; (b) increased number of TRAP (tartrate resistant acid phosphatase), VEGF (vascular endothelial growth factor) cells and the degree of vascularization; and (c) enhanced expression of sympathetic nerve fibers. The structural and cellular changes of osteoporotic periosteum indicate that periosteum plays an important role in the cortical bone resorption in metaphyseal areas and this pathological process may be regulated by the sympathetic nervous system.

Multilineage differentiation potential of bone and cartilage cells derived from explant culture

To date, mesenchymal stem cells (MSCs) from various tissues have been reported, but the yield and differentiation potential of different tissue-derived MSCs is still not clear. This study was undertaken in an attempt to investigate the multilineage stem cell potential of bone and cartilage explant cultures in comparison with bone marrow derived mesenchymal stem cells (BMSCs). The results showed that the surface antigen expression of tissue-derived cells was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing markers related to adhesion (CD29, CD166) and stem cells (CD90, CD105). The tissue-derived cells were able to differentiate into osteoblast, chondrocyte and adipocyte lineage pathways when stimulated in the appropriate differentiating conditions. However, compared with BMSCs, tissue-derived cells showed less capacity for multilineage differentiation when the level of differentiation was assessed in monolayer culture by analysing the expression of tissue-specific genes by reverse transcription polymerase chain reaction (RT-PCR) and histology. In high density pellet cultures, tissue-derived cells were able to differentiate into chondrocytes, expressing chondrocyte markers such as proteoglycans, type II collagen and aggrecan. Taken together, these results indicate that cells derived from tissue explant cultures reserved certain degree of differentiation properties of MSCs in vitro.