Applied nanotechnology in orthopaedic oncology

Nowadays, bone cancer is a major issue especially for young people. Common diagnosis and therapeutic methods are not entirely effective as they lack adequate precision and efficacy. Novel nanostructures have drawn widespread attention due to their broad applications in tumor diagnosis and therapy. In the present review, the impact of nanotechnology in diagnosis and treatment of bone cancer is discussed. A plethora of nanostructures and their applications in diagnosis, treatment as well as in theranostics for bone tumor diagnosis, treatment and regeneration of bone defects is described in order to provide an outlook for all nanoscientists. In addition, reference is made in toxicity of the nanostructures utilized in medical applications. The literature review revealed that nontechnology based methods for imaging and treatment of bone tumor could provide earlier diagnosis and more effective therapy compared with up-to now existing methods. However, the toxicity of nanostructures remains a longstanding challenge for the research community.Nowadays, bone cancer is a major issue especially for young people. Common diagnosis and therapeutic methods are not entirely effective as they lack adequate precision and efficacy. Novel nanostructures have drawn widespread attention due to their broad applications in tumor diagnosis and therapy. In the present review, the impact of nanotechnology in diagnosis and treatment of bone cancer is discussed. A plethora of nanostructures and their applications in diagnosis, treatment as well as in theranostics for bone tumor diagnosis, treatment and regeneration of bone defects is described in order to provide an outlook for all nanoscientists. In addition, reference is made in toxicity of the nanostructures utilized in medical applications. The literature review revealed that nontechnology based methods for imaging and treatment of bone tumor could provide earlier diagnosis and more effective therapy compared with up-to now existing methods. However, the toxicity of nanostructures remains a longstanding challenge for the research community

Preparation and characterization of carrageenan/ halloysite nanotube nanocomposite films for potential transdermal drug delivery application

The attention of using synthetic polymers in medical and pharmaceutical purposes has been drawn towards polysaccharide-based materials due to their inertness, non-toxicity, biocompatibility, biodegradability, low cost and abundant availability. Among polysaccharides, there has been very little work on carrageenan (CRG) as a candidate for transdermal drug delivery patches. Carrageenan is a sulphated polysaccharide with simple gelation mechanism, thermo-reversible ability and tunable viscoelastic properties. Despite its interesting properties and potential, CRG has low mechanical strength and possesses fast drug release rate which lead to fast disintegration of polymer matrix. In this study, a CRG film was prepared by solution casting with the addition of halloysite nanotube (HNT) as reinforcing filler. Significant mechanical improvement of CRG film was achieved at 3 pph loading of HNT with increased tensile strength and elongation at break, and decreasing modulus; optimum strength of 8.54 MPa, elongation percentage of 53.72% and modulus of 13.76 MPa. The CRG/HNT film with 3 pph HNT also showed high swelling capacity (~97%) with longer disintegration time of more than 20 minutes. The morphological observations and Fourier transform infrared (FTIR) spectra confirmed that good dispersion and interactions were achieved between CRG and HNT. The nanocomposite film has better moisture repellent and thermal stability compared to the pure CRG film. The X-ray diffraction (XRD) of the nanocomposite film revealed preferential orientation of the HNT in CRG matrix and increase in the level of crystallinity. The loading of diclofenac sodium (DS) and benzalkonium chloride (BKC) to the HNT separately showed that the position of drug in the HNT was charge dependent. The DS was found to entrap inside the HNT lumen and has better sustainable release than the BKC which deposited mostly onto the external surface of HNT. The Franz diffusion study revealed that the inclusion of HNT minimized the burst effect of both drug models, sustained the release of DS by ~23% after 12 hours and prolonged the complete release of BKC for more than 7 hours. The nanocomposite film with DS possessed a flux (J) of 0.0117 mg/cm2/h and a permeability coefficient (P) of 5.91 x 10-3 cm/h, while the film patch with BKC possessed a J value of 0.0489 mg/cm2/h and a P value of 24.7 x 10-3 cm/h. The release of DS from the patches follows first order kinetic model while the BKC follows zero order kinetic model. The cytotoxicity study indicated improved patch biocompatibility by the HNT addition and the drugs loading induced certain toxicity towards the film patches. Based on these results, the addition of HNT has improved the performance of CRG film as a matrix patch. Therefore, the CRG/HNT film presents potential and feasibility as a material for transdermal drug delivery system

Application of Halloysite Nanotubes in Bone Disease Remediation and Bone Regeneration

Customized patient therapy has been a major research focus in recent years. There are two research fields that have made a significant contribution to realizing individualized-based treatment: targeted drug delivery and three-dimensional (3D) printing technology. With benefit from the advances in nanotechnology and biomaterial science, various drug delivery systems have been established to provide precise control of therapeutic agents release in time and space. The emergence of three-dimensional (3D) printing technology enables the fabrication of complicated structures that effectively mimic native tissues and makes it possible to print patient-specific implants. My dissertation research used a clay nanoparticle, halloysite, to develop a drug delivery system and 3D scaffold which may contribute to individualized-based treatment. Halloysite nanotubes (HNTs) are naturally occurring tubular nanoparticles with a hollow lumen. They possess a high aspect ratio, thermal stability, and unique oppositely charged inner and outer surfaces. These inherent features enable them to be used as a bulk filler to improve the performance characteristics of many polymers. Besides, HNTs are biocompatible and have a demonstrated capacity to delivery growth factors, RNA, DNA and other chemical substances; therefore, HNTs have received extensive attention in the development of drug delivery systems. In this dissertation, HNTs were applied in the development of medical devices for bone disease remediation, tissue regeneration, and restoration of bone function. Osteomyelitis is a bone infection and mainly caused by Staphylococcus aureus (S. aureus). Gentamicin is the antibiotic commonly used to against gram- negative and positive bacteria, which includes S. aureus. When gentamicin was loaded into HNTs and incorporated with chitosan, the hybrid chitosan/HNTs hydrogels provided a sustained drug release and successfully inhibited the growth of S. aureus. Simultaneously, the addition of HNTs improved chitosan mechanical properties. Osteosarcoma is the most common cancer tumor occurring in bone tissue. Through surface modification, HNTs were conjugated with folic acid and fluorochrome (FITC). The bi-functionalized HNTs (bHNTs) were then doped with anticancer drugs, methotrexate (MTX). MTX-doped bHNTs showed a high drug loading efficiency and selectively targeted cancer cells. MTX-loaded bHNTs efficiently inhibited osteosarcoma proliferation without harm to normal type cells (pre-osteoblasts). Osteoporosis is the most common bone disease as the bone formation fails to keep up with the bone resorption rate. Bone fractures happen as a result of long-term bone defection. Three dimensional printed scaffolds that support bone regeneration could be a viable alternative to bone grafting, which is limited by insufficient supplies and issued with infection. Metal-doped HNTs were combined with PLA and printed with a specific pore size and porosity design. After surface modification, 3D printed HNTs/PLA scaffolds encouraged cell adhesion and osteogenic differentiation. Furthermore, surface coating of gentamicin had a long stock life to inhibit bacterial growth and promoted osteogenesis

Nano clay-enhanced calcium phosphate cements and hydrogels for biomedical applications

Biomaterials are used as templates for drug delivery, scaffolds in tissue engineering, grafts in surgeries, and support for tissue regeneration. Novel biomaterial composites are needed to meet multifaceted requirements of compatibility, ease of fabrication and controlled drug delivery. Currently used biomaterials in orthopedics surgeries suffer limitations in toxicity and preventing infections. Polymethyl methacrylate (PMMA) used as bone cement suffers from limitations of thermal necrosis and monomer toxicity calls for development of better cementing biomaterials. A biodegradable/bioresorbable cement with good mechanical properties is needed to address this short coming. Metal implants used in fixing fractures or total joint replacement needs improvements in preventing biofilm formation and better tissue integration. This research addressed the above mentioned research gaps by formulating novel biomaterial composites. Calcium phosphate cements are the alternative bone cements that are bioresorbable and promote tissue integration. These cements lack sufficient mechanical strengths to be used in load bearing sites. The addition of nanoparticles is hypothesized to improve the mechanical properties without inducing toxicity to the tissue. This hypothesis was tested by evaluating compression and flexural strengths in addition to cytocompatibility tests. Results indicate that addition of nano-clay particles (halloysites nanotubes) improved the compressive strength and osteoinductive properties of calcium phosphate cements. To address the research need of preventing implant failure due to infection and aseptic loosening, novel coatings are needed. Hydrogels are well establish for their ability to mimic in vivo environment, promote cell viability and as drug delivery vehicles. Use of composites of hydrogels and drug-loaded nanoparticles to prevent infection was evaluated. Cytocompatibility results indicate good cell viability. Antibacterial results show sustained release of antibiotics from composite hydrogels and good zones of inhibition on agar plates inoculated with bacterial cultures. Fabricating a complex three-dimensional (3D) scaffold for tissue engineering was a huge challenge. With advancements in additive manufacturing, this research gap was addressed. Methods are needed to fabricate patient specific grafts made from biocompatible biomaterials. In this research, 3D printing was used as a platform to explore new biomaterials as grafts or scaffolds for tissue engineering. Computerized tomography scans were used to fabricate patient-specific grafts. The use of calcium cements to fabricate three-dimensionally complex scaffold or grafts reported in this research holds potential in personalized medicine

Historical Wood: Structure, Properties and Conservation

This book is a selection of manuscripts devoted to the conservation and preservation of wooden cultural heritage. The articles present the new methods for conservation of various historical wooden artefacts, reliable modern techniques for characterisation of the wood structure, properties and degree of degradation, and discusses problems and doubts related to all aspects of conservation and re-conservation of wooden cultural heritage. It contains both review and research papers to give the readers a broader picture of the problems and issues related to the conservation of wooden historical objects and structures. We need to remember that wooden cultural heritage is an integral part of our culture and history that define our humanity. We are obliged to protect it, save it from oblivion, and preserve it for future generations