INVESTIGATION ON STRUCTURE AND PROPERTIES OF BIOACTIVE GLASS MATERIALS FOR THERAPEUTIC APPLICATIONS

Abstract

The primary purpose of biomaterials is to substitute tissues that are infected, injured, or damaged. The initial biomaterials used were bioinert, aiming to minimize the formation of scar tissue at the interface between the implant and the tissue. Dr. Larry Hench discovered Bioglass in 1969, which possesses the ability to bond with bone without being surrounded by fibrous tissues. It has been observed that Bioglass exhibits a significantly greater bonding capacity than other biomaterials. Its capability to generate hydroxyapatite with body fluid renders it unparalleled when compared to hydroxyapatite crystals. Besides providing a platform for cell development, the presence of silicon ions serves as a catalyst to accelerate cellular proliferation. Recent findings indicate that Bioglass is not only suitable for hard tissue regeneration but can also be applied beyond bone regeneration, such as in soft tissue engineering. Since the late 1960s, various techniques, including the melt- quench method, the sol-gel method, flame spray synthesis, microwave synthesis, and others, have been developed for Bioglass formation. Additionally, a novel, cost-effective, environmentally friendly synthetic approach known as the bioinspired route was introduced by Santhiya et al. in 2013. This method draws inspiration from naturally synthesized nanostructured materials like silica in diatoms, following the guidance of biomacromolecule templates. Over the past two decades, bio-inspired synthesis of nanostructured ceramic oxides below 100°C has been well-established using organic templates. Santhiya et al. investigated the impact of various templates on the textural and morphological properties of Bioglass particles. In this current study, magnetic nanoparticles were templated on BG NPs, thus developing magnetism in BG. Further we developed PTAs showing luminescence and magnetic properties in BG which are mesoporous in nature. In this thesis, considering the huge importance of bioactive glass hybrid materials for both soft and hard tissue 10 engineering applications, various in-situ mineralized bioactive glass hybrid materials are synthesized and characterized in detail. This thesis has been summarized in 4 chapters. Chapter 1 gives a broad overview of biomaterial generations, bioactive glass as a third-generation biomaterial in soft and hard tissue engineering, and applications of bioglass beyond bone regeneration. Furthermore, a comprehensive review of research on the synthesis of bioactive glass and the mechanism of bioactivity in simulated body fluid is presented. Synthetic techniques for doped magnetic and non-magnetic bioactive glasses are briefly described, along with their importance in biological applications. Chapter 2 Multiple biological advances have made use of bioactive glass (BG) nanoparticles (NPs) in regenerative medicine, bone and tooth repair, drug and gene transfer, cancer treatment, and cosmetics. Normal biocompatible coatings alongside hydrocarbons, polymers, and silica significantly affect fundamental attributes of NPs. In this study, we synthesized a novel mesoporous BG NPs with magnetite core shell (AMAG_BG) using L-arginine as a template processing magnetic hyperthermia (MH). BG network coverage on magnetite (AMAG) NPs were orchestrated first time by bio-inspired synthesis in watery dissolvable. AMAG and AMAG_BG NPs were characterized by utilizing FE-SEM, HR-TEM, and BET analysis. The elemental composition of L-arginine templated magnetite (AMAG) and AMAG_BG NPs was also determined by XPS and EDX analysis. Characteristics of AMAG_BG were contrasted with bare AMAG NPs in morphology, particle size, porosity, and composition. The fabricated BG NPs' in-vitro bioactivity and heat studies were successfully monitored after interaction with simulated bodily fluid (SBF). Magnetic studies and in-vitro heat studies together demonstrated the behavior of BG NPs towards MH treatment of cancerous cells. Cytotoxicity tests on AMAG_BG NPs using U2OS and human blood cells with appropriate control experiments revealed 11 biocompatibility. The study represents magnetic and thermal property-dependent sustainable synthetic process of AMAG_BG NPs for cancer treatment. Chapter 3 The nanosized 45S5 bioactive glass (BG) containing iron (Fe) and bismuth (Bi) as magnetic photothermal agent (PTA) (B_F_FABG) was first time synthesized by Bio-inspired route using folic acid (FA) template. Similarly, for a comparative analysis, BG doped with Fe/Bi separately (F_FABG and B_FABG) were also synthesized. XPS and FTIR analysis of B_F_FABG revealed the presence of folic acid (FA) and dopants Fe and Bi in the BG network. Based on the XRD pattern, B_F_FABG was semi-crystalline in nature, with an average crystallite size of 0.2 ± 0.04 nm. Fe ions and FA molecules have a lower affinity for the BG network than the heaviest and most polarizable Bi ions, according to TGA analysis. An increase of Q4 species in B_F_FABG network was revealed by 29Si NMR investigation, due to the presence of Fe and Bi ions. For B_F_FABG, there was also a rise in Q3 and Q2 species due to the dual dopants. B_F_FABG is nano-crystalline, with an average diameter of 12.8 ± 0.3 nm, according to HR-TEM and SAED pattern. The BG samples, both doped and undoped, were found to be mesoporous, with pore diameters ranging from 2 nm to 50 nm. Due to the presence of Bi ions, B_F_FABG showed remarkable photoluminescence along with bone bonding ability during excitation in the range of ~1092 nm. The magnetic characteristics were also induced in B_F_FABG due to Fe doping. The novel B_F_FABG NPs reported least toxicity through in-vitro haemolysis assay and is an ultimate multifunctional material to treat bone abnormalities. Chapter 4 The current study focused to synthesize magnesium (Mg2+) and bismuth (Bi3+) co-doped bioactive glass (BG) nanoparticles (NPs) at ambient conditions. Curcumin (CC) a therapeutic agent was used as a template to synthesize BG NPs along with 1 mol% MgO and increasing amount of Bi2O3 (From 0.5 mol% to 1.5 mol%). XPS confirmed the presence of doped elements in BG samples. 12 XRD reported an increase in mean crystallite size that was from 0.1 ± 0.02 nm to 0.3 ± 0.02 nm with the increase in Bi3+ ions concentration, which has metallic nature. The FTIR study confirmed silicate network development in CCBG with CC template and largely highlights the Si–O–Bi stretching vibrations. TGA revealed that co-doping of Mg2+ and Bi3+ to the BG samples increased their thermal stability in comparison to the control. Co-doping in BG NPs indicated more open SiO2 network as depicted by NMR. FE-SEM and HR-TEM along with SAED pattern confirmed that co-doped BG NPs were nanosized with increased crystallinity with increasing Bi3+ concentration. The optical transmittance behaviour showed a strong emission peak at 480 nm with decreased intensity with increasing Bi3+ ion concentration. Co-doped BG NPs were found to be mesoporous, with pore diameters ranging from 2 nm to 50 nm according to BET analysis. In-vitro bioactivity revealed excellent bone bonding ability of BG. The novel co-doped BG reported least toxicity and excellent biocompatibility through in-vitro haemolysis assay and MTT assay.