Chronic Leg Ulcers: Are Tissue Engineering and Biomaterials Science the Solution?

Chronic leg ulcers (CLUs) are full thickness wounds that usually occur between the ankle and knee, fail to heal after 3 months of standard treatment, or are not entirely healed at 12 months. CLUs present a considerable burden on patients, subjecting them to severe pain and distress, while healthcare systems suffer immense costs and loss of resources. The poor healing outcome of the standard treatment of CLUs generates an urgent clinical need to find effective solutions for these wounds. Tissue Engineering and Biomaterials Science offer exciting prospects for the treatment of CLUs, using a broad range of skin substitutes or scaffolds, and dressings. In this review, we summarize and discuss the various types of scaffolds used clinically in the treatment of CLUs. Their structure and therapeutic effects are described, and for each scaffold type representative examples are discussed, supported by clinical trials. Silver dressings are also reviewed due to their reported benefits in the healing of leg ulcers, as well as recent studies on new dermal scaffolds, reporting on clinical results where available. We conclude by arguing there is a further need for tissue-engineered products specifically designed and bioengineered to treat these wounds and we propose a series of properties that a biomaterial for CLUs should possess, with the intention of focusing efforts on finding an effective treatment

Extracción de características y clasificación automática de señales de audio

The purpose it is to make the development of an algorithm that is able to extract the features of audio segments for further classification in speech, music or music and speech files. For this we have analysed the most referenced classification algorithms in the literature, and their characteristics, performance and computational complexity evaluated during training and recognition phases. From these studies, it has been decided to implement a system based on low-level features and a statistical classifier system. MATLAB has been chosen as the development tool since the applications in mind did not require a real-time training system. The coefficients we use to characterize the different types of signal are called MFCC, an acronym for the Mel Frequency Cepstral Coefficient. And as training algorithm a Gaussian Mixture Model (GMM) will be used for each audio class, which will change the number of Gaussians to model and will evaluate the best configuration. In addition to the MFCC, we will also implement the MFCC Deltas and MFCC Delta-Deltas that will provide us with information about the dynamic properties of audio; because MFCC only provide information within a window where the signal is considered stationary. As discussed below, the obtained results are enough satisfactory for the algorithm to run on a real case. Charts and graphs of average error rate for the different configurations of inputs that have been tested and reported. The results information is expanded in the annex

The effect of temperature on the viability of human mesenchymal stem cells

Introduction Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. Methods The viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett’s test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue). Results Results showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group. Conclusions The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations

Decellularization of tumours: A new frontier in tissue engineering

Cancer is one of the leading causes of death worldwide. The tumour extracellular matrix (ECM) has unique features in terms of composition and mechanical properties, resulting in a structurally and chemically different ECM to that of native, healthy tissues. This paper reviews to date the efforts into decellularization of tumours, which in the authors’ view represents a new frontier in the ever evolving field of tumour tissue engineering. An overview of the ECM and its importance in cancer is given, ending with examples of research using decellularized tumours, which has already indicated potential therapeutic targets, unravelled malignancy mechanisms or response to chemotherapy agents. The review highlights that more research is needed in this area, which can answer important questions related to tumour formation and progression to ultimately identify new and effective therapeutic targets. Within the near-future of personalized medicine, this research can create patient-specific tumour models and therapeutic regimes

Development of a bone tissue-engineered construct to enhance new bone formation in revision total hip replacement

The main issue associated with revision total hip replacements (rTHRs) is how to generate new bone and restore bone stock for fixation of the revision stem. Bone tissue engineering (BTE) seeks the generation of constructs ex vivo in order to replace damaged or lost bone. The aim of this thesis was to develop a bone tissue-engineered construct with a calcium-phosphate (CaP) coated porous metal scaffold seeded throughout its structure with mesenchymal stem cells (MSCs) in order to enhance new bone formation at rTHRs. The study had in vitro and in vivo phases. For the in vitro phase, CaP coatings by biomimetic and electrochemical methods on the surface of titanium and tantalum discs were investigated and seeded with MSCs under static culture conditions. Different coating methods produced different morphologies and compositions with biomimetic coatings enhancing MSCs growth while the electrochemical ones enhanced their osteogenic potential. An electrochemically CaP coated porous titanium cylinder was seeded with MSCs and dynamically cultured in a perfusion bioreactor, showing an increased MSCs proliferation and osteogenic differentiation and an even distribution of cells throughout the scaffolds compared to statically cultured constructs. Tissue-engineered constructs in the perfusion bioreactor were evaluated in vivo by implantation in the medial femoral condyle of sheep with and without gap. Their osseointegration and implant-bone fixation strength were compared to non tissue-engineered constructs. The results showed that the addition of MSCs to the scaffolds did not significantly increase osseointegration or implant-bone fixation strength. However, in the defects with gap the tissue-engineered constructs showed a higher implant-bone contact area and therefore higher forces were necessary to push the tissue-engineered implants out of the bone in the defects with gap than for the non tissue-engineered ones. In conclusion, BTE can be applied in order to develop constructs with a clinical application in rTHRs where a lack of bone stock is problematic

Where we live matters: child development and informal settlements

The assertion ‘where we live matters’ (Braveman, Cubbin, Egerter, and Pedregon, 2008:1) is particularly important for the attainment of the healthy and sustainable living environment that is ideal for child development. According to child developmentalists, physical and social environmental factors play a crucial role in child development. Today, the majority of children, who make up almost half of the urban population in the Third World cities, live in the informal settlements. Informal settlements have always been associated with negative child developmental outcomes. By linking the physical and social environmental factors that influence child development reviewed in the child development literature to the living environments in informal settlements, this research report reveals that there are both positive and negative child developmental outcomes emanating from informal settlements. However, the positive aspects are often disrupted due to governments’ negligence to provide essential services to informal settlements coupled with limited reference to child developmental issues in informal settlements intervention paradigms. This research calls for governments and policy makers to develop strategies that complement the positive aspects of informal settlements for the attainment of healthy and sustainable physical and social environments required for children to develop to their full potential

Biofilm formation in total hip arthroplasty: Prevention and treatment

Biomaterials science is a very active area of research, which has allowed the successful use of implants in the orthopaedic field for over a century. However, implant infection remains a clinical concern as it is associated with extensive patient morbidity and a high economic burden, which is predicted to increase due to an ageing population. Bacteria are able to adhere, colonise and develop into biofilms on the surface of biomaterials making associated infections physiologically different to other post-surgical infections. Unfortunately, biofilms exert increased protection from the host immune system and an increased resistance to antibiotic therapy in comparison to their planktonic counterparts. The aim of this review is to assess the current knowledge on treatments, pathogenesis and the prevention of infections associated with orthopaedic implants, with a focus on total hip arthroplasty

A bone-on-a-chip collagen hydrogel-based model using pre-differentiated adipose-derived stem cells for personalized bone tissue engineering

Mesenchymal stem cells have contributed to the continuous progress of tissue engineering and regenerative medicine. Adipose-derived stem cells (ADSC) possess many advantages compared to other origins including easy tissue harvesting, self-renewal potential, and fast population doubling time. As multipotent cells, they can differentiate into osteoblastic cell linages. In vitro bone models are needed to carry out an initial safety assessment in the study of novel bone regeneration therapies. We hypothesized that 3D bone-on-a-chip models containing ADSC could closely recreate the physiological bone microenvironment and promote differentiation. They represent an intermedium step between traditional 2D–in vitro and in vivo experiments facilitating the screening of therapeutic molecules while saving resources. Herein, we have differentiated ADSC for 7 and 14 days and used them to fabricate in vitro bone models by embedding the pre-differentiated cells in a 3D collagen matrix placed in a microfluidic chip. Osteogenic markers such as alkaline phosphatase activity, calcium mineralization, changes on cell morphology, and expression of specific proteins (bone sialoprotein 2, dentin matrix acidic phosphoprotein-1, and osteocalcin) were evaluated to determine cell differentiation potential and evolution. This is the first miniaturized 3D-in vitro bone model created from pre-differentiated ADSC embedded in a hydrogel collagen matrix which could be used for personalized bone tissue engineering

The effect of temperature on the viability of human mesenchymal stem cells

Introduction Impaction allograft with cement is a common technique used in revision hip surgeries for the last 20 years. However, its clinical results are inconsistent. Recent studies have shown that mesenchymal stem cells (MSCs) seeded onto allograft can enhance bone formation. This in vitro study investigates whether the increase in temperature related to the polymerisation of bone cement will affect the viability of human MSCs. Methods The viability of human MSCs was measured after incubating them at temperatures of 38°C, 48°C and 58°C; durations 45 seconds, 80 seconds and 150 seconds. A control group was kept at 37°C and 5% carbon dioxide for the duration of the investigation (7 days). During the course of the study the human MSCs were analysed for cell metabolic activity using the alamarBlue™ assay, cell viability using both Trypan Blue dye exclusion and calcein staining under fluorescent microscopy, and necrosis and apoptosis using Annexin V and propidium iodide for flow cytometric analysis. A one-way analysis of variance with a priori Dunnett’s test was used to indicate the differences between the treatment groups, when analysed against the control. This identified conditions with a significant difference in cell metabolic activity (alamarBlue™) and cell viability (Trypan Blue). Results Results showed that cell metabolism was not severely affected up to 48°C/150 seconds, while cells in the 58°C group died. Similar results were shown using Trypan Blue and calcein analysis for cell viability. No significant difference in apoptosis and necrosis of the cells was observed when human MSCs treated at 48°C/150 seconds were compared with the control group. Conclusions The study suggests that human MSCs seeded onto allograft can be exposed to temperatures up to 48°C for 150 seconds. Exposure to this temperature for this time period is unlikely to occur during impaction allograft surgery when cement is used. Therefore, in many situations, the addition of human MSCs to cemented impaction grafting may be carried out without detrimental effects to the cells. Furthermore, previous studies have shown that this can enhance new bone formation and repair the defects in revision situations