Reempowering ourselves: Australian Aboriginal women

The arrival of the colonists, the invasion of Aboriginal lands and the subsequent colonization of Australia had a disastrous effect on Aboriginal women, including on-going dispossession and disempowerment. Aboriginal women’s lives and gendered realities were forever changed in most communities. The system of colonization deprived Aboriginal women of land and personal autonomy and restricted the economic, political, social, spiritual and ceremonial domains that had existed prior to colonization. It also involved the implementation of overriding patriarchal systems. This is why Aboriginal women may find understanding within the women’s movement and why feminism might offer them a source of analysis. There are some connections in the various forms of social oppression, which give women connection and a sharing on some issues. However, imperialism and colonialism are also part of the women’s movement and feminism. This essay demonstrates why attempts to engage with feminism and to be included in women-centred activities might result in the denial and sidelining of Aboriginal sovereignty and further oppression and marginalisation of Aboriginal women. Moreover, strategies employed by non-Indigenous feminists can result in the maintenance of white women’s values and privileges within the dominant patriarchal white society. By engaging in these strategies feminists can also act in direct opposition to Aboriginal sovereignty and Aboriginal women. This essay states clearly that women who do not express positions or opinions in outright support of these activities still benefit from their position by proxy and contribute to the cultural dominance of non-Indigenous women. I argue that Aboriginal women need to define what empowerment might mean to themselves, and I suggest re-empowerment as an act of Aboriginal women’s healing and resistance to the on-going processes and impacts of colonization.

Factors associated with recurrence of venous leg ulcers : a survey and retrospective chart review

Background: Chronic venous leg ulcers have a significant impact on older individuals’ well-being and health care resources. Unfortunately after healing, up to 70% recur. ----- Objective: To examine the relationships between leg ulcer recurrence and physical activity, compression, nutrition, health, psychosocial indicators and self-care activities in order to provide information for preventive strategies. ----- Design: Survey and retrospective chart review Settings: Two metropolitan hospital and three community-based leg ulcer clinics. ----- Subjects: A sample of 122 community living patients with leg ulcer of venous aetiology which had healed between 12 and 36 months prior to the survey. ---- Methods: Data were collected from medical records on demographics, medical history and previous ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer recurrences and history, compression and other self-care activities. All variables significantly associated with recurrence at the bivariate level were entered into a logistic regression model to determine their independent influences on recurrence. ----- Results: Median follow-up time was 24 months (range 12–40 months). Sixty-eight percent of participants had recurred. Bivariate analysis found recurrence was positively associated with ulcer duration, cardiac disease, a Body Mass Index ≤20, scoring as at-risk of malnutrition and depression; and negatively associated with increased physical activity, leg elevation, wearing Class 2 (20–25mmHg) or Class 3 (30–40mmHg) compression hosiery, and higher self-efficacy scores. After adjusting for all variables, an hour/day of leg elevation (OR=0.04, 95% CI=0.01–0.17), days/week in Class 2 or 3 compression hosiery (OR=0.53, 95% CI=0.34–0.81), Yale Physical Activity Survey score (OR=0.95, 95% CI=0.92–0.98), cardiac disease (OR=5.03, 95% CI=1.01–24.93) and General Self-Efficacy scores (OR=0.83, 95% CI=0.72–0.94) remained significantly associated (p<0.05) with recurrence. ----- Conclusions: Results indicate a history of cardiac disease is a risk factor for recurrence; while leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence.

Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critically-sized femoral defects

The repair of large non-unions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause bone marrow stromal cells to lose their differentiation ability. To overcome these limitations, we have genetically engineered bone marrow stromal cells to constitutively overexpress the osteoblast specific transcription factor Runx2. In the present study, we examined Runx2-modified bone marrow stromal cells, delivered via poly(caprolactone) scaffolds loaded with type I collagen meshes, in critically-sized segmental defects in rats compared to unmodified cells, cell-free scaffolds and empty defects. Runx2 expression in bone marrow stromal cells accelerated healing of critically-sized defects compared to unmodified bone marrow stromal cells and defects receiving cell-free treatments. These findings provide an accelerated method for healing large bone defects which may reduce recovery time and the need for external fixation of critically-sized defects.

Enhancing in vivo vascularized bone formation by cobalt chloride-treated bone marrow stromal cells in a tissue engineered periosteum model

The periosteum plays an indispensable role in both bone formation and bone defect healing. In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl(2))-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularization. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT, histomorphometrical and immunohistochemical methods. The results showed that CoCl(2) pre-treated BMSCs induced higher degree of vascularization and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.

Bioactive mesopore-glass microspheres with controllable protein-delivery properties by biomimetic surface modification

Microsphere systems with the ideal properties for bone regeneration need to be bioactive, and at the same time possess the capacity for controlled protein/drug-delivery; however, the current crop of microsphere system fails to fulfill these properties. The aim of this study was to develop a novel protein-delivery system of bioactive mesoporous glass (MBG) microspheres by a biomimetic method through controlling the density of apatite on the surface of microspheres, for potential bone tissue regeneration. MBG microspheres were prepared by using the method of alginate cross-linking with Ca2+ ions. The cellular bioactivity of MBG microspheres was evaluated by investigating the proliferation and attachment of bone marrow stromal cell (BMSC). The loading efficiency and release kinetics of bovine serum albumin (BSA) on MBG microspheres were investigated after coprecipitating with biomimetic apatite in simulated body fluids (SBF). The results showed that MBG microspheres supported BMSC attachment and the Si containing ionic products from MBG microspheres stimulated BMSCs proliferation. The density of apatite on MBG microspheres increased with the length of soaking time in SBF. BSA-loading efficiency of MBG was significantly enhanced by co-precipitating with apatite. Furthermore, the loading efficiency and release kinetics of BSA could be controlled by controlling the density of apatite formed on MBG microspheres. Our results suggest that MBG microspheres are a promising protein-delivery system as a filling material for bone defect healing and regeneration.

Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model

This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 lg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3-month period as determined by microcomputed tomography (lCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factorbased therapies.

Meniscal repair in the elite athlete : results of 45 repairs with a minimum 5-year follow-up

Background The preservation of meniscal tissue is important to protect joint surfaces. Purpose We have an aggressive approach to meniscal repair, including repairing tears other than those classically suited to repair. Here we present the medium- to long-term outcome of meniscal repair (inside-out) in elite athletes. Study Design Case series; Level of evidence, 4. Methods Forty-two elite athletes underwent 45 meniscal repairs. All repairs were performed using an arthroscopically assisted inside-out technique. Eighty-three percent of these athletes had ACL reconstruction at the same time. Patients returned a completed questionnaire (including Lysholm and International Knee Documentation Committee [IKDC] scores). Mean follow-up was 8.5 years. Failure was defined by patients developing symptoms of joint line pain and/or locking or swelling requiring repeat arthroscopy and partial meniscectomy. Results The average Lysholm and subjective IKDC scores were 89.6 and 85.4, respectively. Eighty-one percent of patients returned to their main sport and most to a similar level at a mean time of 10.4 months after repair, reflecting the high level of ACL reconstruction in this group. We identified 11 definite failures, 10 medial and 1 lateral meniscus, that required excision; this represents a 24% failure rate. We identified 1 further patient who had possible failed repairs, giving a worst-case failure rate of 26.7% at a mean of 42 months after surgery. However, 7 of these failures were associated with a further injury. Therefore, the atraumatic failure rate was 11%. Age and size and location of the tears were not associated with a higher failure rate. Medial meniscal repairs were significantly more likely to fail than lateral meniscal repairs, with a failure rate of 36.4% and 5.6%, respectively (P < .05). Conclusion Meniscal repair and healing are possible, and most elite athletes can return to their preinjury level of activity.

A hydrogen tethered inhibitor of matrix metalloproteinases

During wound repair, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors (the TIMPs) is crucial for the normal extra cellular matrix turnover. However, the over expression of several MMPs including MMP-1, 2, 3, 8, 9 and MMP-10, combined with abnormally high levels of activation or low expression of TIMPs, may contribute to excessive degradation of connective tissue and formation of chronic ulcers. There are many groups exploring strategies for promoting wound healing involving delivery of growth factors, cells, ECM components and small molecules. Our approach for improving the balance of MMPs is not to add anything more to the wound, but instead to neutralise the over-expressed MMPs using inhibitors tethered to a bandage-like hydrogel. Our in vitro experiments using designed synthetic pseudo peptide inhibitors have been demonstrated to inhibit MMP activity in standard solutions. These inhibitors have also been tethered to polyethylene glycol hydrogels using a facile reaction between the linker unit on the inhibitor and the gel. After tethering the inhibition of MMPs diminishes to some extent and we postulate that this arises due to poor diffusion of the MMPs into the gels. When the tethered inhibitors were tested against chronic wound fluid obtained against patients we observed over 40% inhibition in proteolytic activity suggesting our approach may prove useful in rebalancing MMPs within chronic wounds.

A new future for growth factor complexes as wound therapies?

Background: Topical administration of growth factors (GFs) has displayed some potential in wound healing, but variable efficacy, high doses and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple GFs and extracellular matrix (ECM) proteins. The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring. Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury. Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used. Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

The impact of psychosocial factors on adherence to compression therapy to prevent recurrence of venous leg ulcers

Aims To identify self-care activities undertaken and determine relationships between self-efficacy, depression, quality of life, social support and adherence to compression therapy in a sample of patients with chronic venous insufficiency. Background Up to 70% of venous leg ulcers recur after healing. Compression hosiery is a primary strategy to prevent recurrence, however, problems with adherence to this strategy are well documented and an improved understanding of how psychosocial factors influence patients with chronic venous insufficiency will help guide effective preventive strategies. Design Cross-sectional survey and retrospective medical record review. Method All patients previously diagnosed with a venous leg ulcer which healed between 12–36 months prior to the study were invited to participate. Data on health, psychosocial variables and self-care activities were obtained from a self-report survey and data on medical and previous ulcer history were obtained from medical records. Multiple linear regression modelling was used to determine the independent influences of psychosocial factors on adherence to compression therapy. Results In a sample of 122 participants, the most frequently identified self-care activities were application of topical skin treatments, wearing compression hosiery and covering legs to prevent trauma. Compression hosiery was worn for a median of 4 days/week (range 0–7). After adjustment for all variables and potential confounders in a multivariable regression model, wearing compression hosiery was found to be significantly positively associated with participants’ knowledge of the cause of their condition (p=0.002), higher self-efficacy scores (p=0.026) and lower depression scores (p=0.009). Conclusion In this sample, depression, self-efficacy and knowledge were found to be significantly related to adherence to compression therapy. Relevance to clinical practice These findings support the need to screen for and treat depression in this population. In addition, strategies to improve patient knowledge and self-efficacy may positively influence adherence to compression therapy.

Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs

The aim of this study was to evaluate the healing of class III furcation defects following transplantation of autogenous periosteal cells combined with b-tricalcium phosphate (b-TCP). Periosteal cells obtained from Beagle dogs’ periosteum explant cultures, were inoculated onto the surface of b-TCP. Class III furcation defects were created in the mandibular premolars. Three experimental groups were used to test the defects’ healing: group A, b-TCP seeded with periosteal cells were transplanted into the defects; group B, b-TCP alone was used for defect filling; and group C, the defect was without filling materials. Twelve weeks post surgery, the tissue samples were collected for histology, immunohistology and X-ray examination. It was found that both the length of newly formed periodontal ligament and the area of newly formed alveolar bone in group A, were significantly increased compared with both group B and C. Furthermore, both the proportion of newly formed periodontal ligament and newly formed alveolar bone in group A were much higher than those of group B and C. The quantity of cementum and its percentage in the defects (group A) were also significantly higher than those of group C. These results indicate that autogenous periosteal cells combined with b-TCP application can improve periodontal tissue regeneration in class III furcation defects.

Physiological investigation of periosteum structure and its application in periosteum tissue engineering

Although many different materials, techniques and methods, including artificial or engineered bone substitutes, have been used to repair various bone defects, the restoration of critical-sized bone defects caused by trauma, surgery or congenital malformation is still a great challenge to orthopedic surgeons. One important fact that has been neglected in the pursuit of resolutions for large bone defect healing is that most physiological bone defect healing needs the periosteum and stripping off the periosteum may result in non-union or non-healed bone defects. Periosteum plays very important roles not only in bone development but also in bone defect healing. The purpose of this project was to construct a functional periosteum in vitro using a single stem cell source and then test its ability to aid the repair of critical-sized bone defect in animal models. This project was designed with three separate but closely-linked parts which in the end led to four independent papers. The first part of this study investigated the structural and cellular features in periostea from diaphyseal and metaphyseal bone surfaces in rats of different ages or with osteoporosis. Histological and immunohistological methods were used in this part of the study. Results revealed that the structure and cell populations in periosteum are both age-related and site-specific. The diaphyseal periosteum showed age-related degeneration, whereas the metaphyseal periosteum is more destructive in older aged rats. The periosteum from osteoporotic bones differs from normal bones both in terms of structure and cell populations. This is especially evident in the cambial layer of the metaphyseal area. Bone resorption appears to be more active in the periosteum from osteoporotic bones, whereas bone formation activity is comparable between the osteoporotic and normal bone. The dysregulation of bone resorption and formation in the periosteum may also be the effect of the interaction between various neural pathways and the cell populations residing within it. One of the most important aspects in periosteum engineering is how to introduce new blood vessels into the engineered periosteum to help form vascularized bone tissues in bone defect areas. The second part of this study was designed to investigate the possibility of differentiating bone marrow stromal cells (BMSCs) into the endothelial cells and using them to construct vascularized periosteum. The endothelial cell differentiation of BMSCs was induced in pro-angiogenic media under both normoxia and CoCl2 (hypoxia-mimicking agent)-induced hypoxia conditions. The VEGF/PEDF expression pattern, endothelial cell specific marker expression, in vitro and in vivo vascularization ability of BMSCs cultured in different situations were assessed. Results revealed that BMSCs most likely cannot be differentiated into endothelial cells through the application of pro-angiogenic growth factors or by culturing under CoCl2-induced hypoxic conditions. However, they may be involved in angiogenesis as regulators under both normoxia and hypoxia conditions. Two major angiogenesis-related growth factors, VEGF (pro-angiogenic) and PEDF (anti-angiogenic) were found to have altered their expressions in accordance with the extracellular environment. BMSCs treated with the hypoxia-mimicking agent CoCl2 expressed more VEGF and less PEDF and enhanced the vascularization of subcutaneous implants in vivo. Based on the findings of the second part, the CoCl2 pre-treated BMSCs were used to construct periosteum, and the in vivo vascularization and osteogenesis of the constructed periosteum were assessed in the third part of this project. The findings of the third part revealed that BMSCs pre-treated with CoCl2 could enhance both ectopic and orthotopic osteogenesis of BMSCs-derived osteoblasts and vascularization at the early osteogenic stage, and the endothelial cells (HUVECs), which were used as positive control, were only capable of promoting osteogenesis after four-weeks. The subcutaneous area of the mouse is most likely inappropriate for assessing new bone formation on collagen scaffolds. This study demonstrated the potential application of CoCl2 pre-treated BMSCs in the tissue engineering not only for periosteum but also bone or other vascularized tissues. In summary, the structure and cell populations in periosteum are age-related, site-specific and closely linked with bone health status. BMSCs as a stem cell source for periosteum engineering are not endothelial cell progenitors but regulators, and CoCl2-treated BMSCs expressed more VEGF and less PEDF. These CoCl2-treated BMSCs enhanced both vascularization and osteogenesis in constructed periosteum transplanted in vivo.

Modelling of some biological materials using continuum mechanics

Continuum mechanics provides a mathematical framework for modelling the physical stresses experienced by a material. Recent studies show that physical stresses play an important role in a wide variety of biological processes, including dermal wound healing, soft tissue growth and morphogenesis. Thus, continuum mechanics is a useful mathematical tool for modelling a range of biological phenomena. Unfortunately, classical continuum mechanics is of limited use in biomechanical problems. As cells refashion the �bres that make up a soft tissue, they sometimes alter the tissue's fundamental mechanical structure. Advanced mathematical techniques are needed in order to accurately describe this sort of biological `plasticity'. A number of such techniques have been proposed by previous researchers. However, models that incorporate biological plasticity tend to be very complicated. Furthermore, these models are often di�cult to apply and/or interpret, making them of limited practical use. One alternative approach is to ignore biological plasticity and use classical continuum mechanics. For example, most mechanochemical models of dermal wound healing assume that the skin behaves as a linear viscoelastic solid. Our analysis indicates that this assumption leads to physically unrealistic results. In this thesis we present a novel and practical approach to modelling biological plasticity. Our principal aim is to combine the simplicity of classical linear models with the sophistication of plasticity theory. To achieve this, we perform a careful mathematical analysis of the concept of a `zero stress state'. This leads us to a formal de�nition of strain that is appropriate for materials that undergo internal remodelling. Next, we consider the evolution of the zero stress state over time. We develop a novel theory of `morphoelasticity' that can be used to describe how the zero stress state changes in response to growth and remodelling. Importantly, our work yields an intuitive and internally consistent way of modelling anisotropic growth. Furthermore, we are able to use our theory of morphoelasticity to develop evolution equations for elastic strain. We also present some applications of our theory. For example, we show that morphoelasticity can be used to obtain a constitutive law for a Maxwell viscoelastic uid that is valid at large deformation gradients. Similarly, we analyse a morphoelastic model of the stress-dependent growth of a tumour spheroid. This work leads to the prediction that a tumour spheroid will always be in a state of radial compression and circumferential tension. Finally, we conclude by presenting a novel mechanochemical model of dermal wound healing that takes into account the plasticity of the healing skin.

Clonal characterization of bone marrow derived stem cells and their application for bone regeneration

Tissue engineering allows the design of functionally active cells within supportive bio-scaffolds to promote the development of new tissues such as cartilage and bone for the restoration of pathologically altered tissues. However, all bone tissue engineering applications are limited by a shortage of stem cells. The adult bone marrow stroma contains a subset of nonhematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). BMSCs are of interest because they are easily isolated from a small aspirate of bone marrow and readily generate single- cell-derived colonies. These cells have the capacity to undergo extensive replication in an undifferentiated state ex vivo. In addition, BMSCs have the potential to develop either in vitro or in vivo into distinct mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Thus, BMSCs are an attractive cell source for tissue engineering approaches. However, BMSCs are not homo- geneous and the quantity of stem cells decreases in the bone marrow in aged population. A sequential loss of lineage differentiation potential has been found in the mixed culture of bone marrow stromal cells due to a heterogenous popu- lation. Therefore, a number of studies have proposed that homogenous bone marrow stem cells can be generated from clonal culture of bone marrow cells and that BMSC clones have the greatest potential for the application of bone regeneration in vivo