High Phosphate Strontium Containing Bioactive Glass Coatings for Bone Tissue Engineering

The need for prosthetic joint implants continues to grow, but many implants fail and require revision surgery, mainly due to non-bonding to bone. Currently many metal prostheses are coated with hydroxyapatite (HA), often giving rise to ceramic particles leading to wear of the prosthesis surface. This thesis describes the development of bioactive glass (BG) coatings for metallic implants to improve the bone-implant bond, enable better osseointegration, and improve implant lifespan. Strontium was substituted for calcium in two series of melt-derived BG based on the SiO2-MgONa2O- K2O-ZnO-P2O5-CaO system. In the first series, 0, 10, 25, 50, 75 and 100% of the CaO was replaced by SrO; and in the second series 10% of the CaO was replaced by SrO and the P2O5 content was varied between 1.07 and 6.42 mol%. Ti alloy coupons were surface coated with BG by enamelling technique. The structural and physical properties of the glasses and glass coatings were investigated by differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Amorphous coatings showed good adhesion to the Ti alloy with the exception of the 100% Srsubstituted coating. The mixed calcium/strontium glasses exhibited a larger processing window; temperature difference between glass transition and onset of crystallization temperature; favouring the production of amorphous well sintered coatings. Dissolution profiles and bioactivity of the produced glasses were investigated by inductively coupled plasma-optical emission spectroscopy (ICP-OES), XRD, NMR and FTIR. Increasing the P2O5 content of the Sr-substituted glasses aided the formation of the hydroxycarbonate apatite (HCA) layer in SBF. 31P and 29Si NMR showed that the glasses were phase separated with a predominantly Q2 silicate structure co-existing with phosphorus in a predominantly Q0 orthophosphate environment. The Q2 silicate structure in the network did not change with substitution of SrO for CaO. LIVE/DEAD staining of human osteosarcoma cells (Saos-2) seeded onto BG coatings indicated that the coatings were not cytotoxic. SEM imaging showed that the cells attached and spread over the coating surface. The degree of osseointegration of the high-phosphate Sr-contatining (50% of the CaO replaced by SrO) BG-coated implants were compared with HA-coated implants up to 24 weeks which were inserted into lapine long bones (distal femur, proximal tibia). High-phosphate Sr-containing BGcoated implants demonstrated superior mechanical fixation and increased peri-implant bone formation compared to HA-coated implants. The results presented in this thesis demonstrate the potential of Srsubstituted BGs with high-phosphate content for the coating of metallic joint implants

Differentiation of human endometrial stem cells encapsulated in alginate hydrogel into oocyte-like cells

Introduction: Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells. Methods: We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel. Results: Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells. Conclusion: The production of oocyte-like cells using 3D alginate hydrogel may be viable in vitro approach for replacing gonad tissues and cells

Connecting Primary Health Care: A Comprehensive Pilot Study

The collection of data within the primary health care facilities in Iran is essentially paper-based. It is focused on family’s health, monitoring of non-infectious and infectious diseases. Clearly due to the paper-based nature of the tasks, timely decision making at most can be difficult if not impossible. As part of an on-going electronic health record implementation project at Tehran University of Medical Sciences, for the first time in the region, based on a comprehensive pilot project, four urban healthcare facilities are connected to their headquarters and beyond, covering all aspects of primary health care, for the last four years. Without delving into the technical aspects of its software engineering processes, the progress of the implementation is reported, selection of summarized data is presented, and experience gained thus far are discussed. Four years passed and if time is any important reason to go by, then it is safe to accept that the software architecture and electronic health record structural model implemented are robust and yet extensible. Aims and duration of a pilot study should be clearly defined prior to start and managed till its completion. Resistance to change and particularly to information technology, apart from its technical aspects, is also based on human factors

High phosphate strontium containing bioactive glass coatings for bone tissue engineering

The need for prosthetic joint implants continues to grow, but many implants fail and require revision surgery, mainly due to non-bonding to bone. Currently many metal prostheses are coated with hydroxyapatite (HA), often giving rise to ceramic particles leading to wear of the prosthesis surface. This thesis describes the development of bioactive glass (BG) coatings for metallic implants to improve the bone-implant bond, enable better osseointegration, and improve implant lifespan. Strontium was substituted for calcium in two series of melt-derived BG based on the SiO2-MgONa2O- K2O-ZnO-P2O5-CaO system. In the first series, 0, 10, 25, 50, 75 and 100% of the CaO was replaced by SrO; and in the second series 10% of the CaO was replaced by SrO and the P2O5 content was varied between 1.07 and 6.42 mol%. Ti alloy coupons were surface coated with BG by enamelling technique. The structural and physical properties of the glasses and glass coatings were investigated by differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Amorphous coatings showed good adhesion to the Ti alloy with the exception of the 100% Srsubstituted coating. The mixed calcium/strontium glasses exhibited a larger processing window; temperature difference between glass transition and onset of crystallization temperature; favouring the production of amorphous well sintered coatings. Dissolution profiles and bioactivity of the produced glasses were investigated by inductively coupled plasma-optical emission spectroscopy (ICP-OES), XRD, NMR and FTIR. Increasing the P2O5 content of the Sr-substituted glasses aided the formation of the hydroxycarbonate apatite (HCA) layer in SBF. 31P and 29Si NMR showed that the glasses were phase separated with a predominantly Q2 silicate structure co-existing with phosphorus in a predominantly Q0 orthophosphate environment. The Q2 silicate structure in the network did not change with substitution of SrO for CaO. LIVE/DEAD staining of human osteosarcoma cells (Saos-2) seeded onto BG coatings indicated that the coatings were not cytotoxic. SEM imaging showed that the cells attached and spread over the coating surface. The degree of osseointegration of the high-phosphate Sr-contatining (50% of the CaO replaced by SrO) BG-coated implants were compared with HA-coated implants up to 24 weeks which were inserted into lapine long bones (distal femur, proximal tibia). High-phosphate Sr-containing BGcoated implants demonstrated superior mechanical fixation and increased peri-implant bone formation compared to HA-coated implants. The results presented in this thesis demonstrate the potential of Srsubstituted BGs with high-phosphate content for the coating of metallic joint implants.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Exploring the various effects of Cu doping in hydroxyapatite nanoparticle

Abstract Adding foreign ions to hydroxyapatite (HAp) is a popular approach for improving its properties. This study focuses on the effects of calcium substitution with copper in HAp. Instead of calcium, copper ions were doped into the structure of hydroxyapatite nanoparticles at 1%, 3%, and 5% concentrations. XRD analysis showed that the amount of substituted copper was less than needed to generate a distinct phase, yet its lattice parameters and crystallinity slightly decreased. Further, the results of degradation tests revealed that copper doping in hydroxyapatite doubled calcium ion release in water. The incorporation of copper into the apatite structure also boosted the HAp zeta potential and FBS protein adsorption onto powders. According to antibacterial investigations, a concentration of 200 mg/ml of hydroxyapatite containing 5% copper was sufficient to effectively eradicate E. coli and S. aureus bacteria. Furthermore, copper improved hydroxyapatite biocompatibility. Alkaline phosphatase activity and alizarin red tests showed that copper in hydroxyapatite did not inhibit stem cell differentiation into osteoblasts. Also, the scratch test demonstrated that copper-containing hydroxyapatite extract increased HUVEC cell migration. Overall, our findings demonstrated the utility of incorporating copper into the structure of hydroxyapatite from several perspectives, including the induction of antibacterial characteristics, biocompatibility, and angiogenesis

Fabrication of hydrogel based nanocomposite scaffold containing bioactive glass nanoparticles for myocardial tissue engineering

Selecting suitable cell sources and angiogenesis induction are two important issues in myocardial tissue engineering. Human endometrial stromal cells (EnSCs) have been introduced as an abundant and easily available resource in regenerative medicine. Bioactive glass is an agent that induces angiogenesis and has been studied in some experiments. The aim of this study was to investigate in vitro differentiation capacity of endometrial stem cells into cardiomyocyte lineage and to evaluate capability of bioactive glass nanoparticles toward EnSCs differentiation into endothelial lineage and angiogenesis on hydrogel scaffold. Our findings suggests that endometrial stem cells could be programmed into cardiomyocyte linage and considered a suitable cell source for myocardial regeneration. This experiment also revealed that inclusion of bioactive glass nanoparticles in hydrogel scaffold could improve angiogenesis through differentiating EnSCs toward endothelial lineage and increasing level of vascular endothelial growth factor secretio