Surface Modification of Biodegradable Porous Mg Bone Scaffold Using Polycaprolactone/Bioactive Glass Composite

A reduction in the degradation rate of magnesium (Mg) and its alloys is in high demand to enable these materials to be used in orthopedic applications. For this purpose, in this paper, a biocompatible polymeric layer reinforced with a bioactive ceramic made of polycaprolactone (PCL) and bioactive glass (BG) was applied on the surface of Mg scaffolds using dip-coating technique under low vacuum. The results indicated that the PCL-BG coated Mg scaffolds exhibited noticeably enhanced bioactivity compared to the uncoated scaffold. Moreover, the mechanical integrity of the Mg scaffolds was improved using the PCL-BG coating on the surface. The stable barrier property of the coatings effectively delayed the degradation activity of Mg scaffold substrates. Moreover, the coatings induced the formation of apatite layer on their surface after immersion in the SBF, which can enhance the biological bone in-growth and block the microcracks and pore channels in the coatings, thus prolonging their protective effect. Furthermore, it was shown that a three times increase in the concentration of PCL-BG noticeably improved the characteristics of scaffolds including their degradation resistance and mechanical stability. Since bioactivity, degradation resistance and mechanical integrity of a bone substitute are the key factors for repairing and healing fractured bones, we suggest that PCL-BG is a suitable coating material for surface modification of Mg scaffolds

Mechanical Properties of Natural Chitosan/Hydroxyapatite/Magnetite Nanocomposites for Tissue Engineering Applications

Chitosan (CS), hydroxyapatite (HA), and magnetite (Fe3O4) have been broadly employed for bone treatment applications. Having a hybrid biomaterial composed of the aforementioned constituents not only accumulates the useful characteristics of each component, but also provides outstanding composite properties. In the present research, mechanical properties of pure CS, CS/HA, CS/HA/magnetite, and CS/magnetite were evaluated by the measurements of bending strength, elastic modulus, compressive strength and hardness values. Moreover, the morphology of the bending fracture surfaces were characterized using a scanning electron microscope (SEM) and an image analyzer. Studies were also conducted to examine the biological response of the human Mesenchymal Stem Cells (hMSCs) on different composites. We conclude that, although all of these composites possess in-vitro biocompatibility, adding hydroxyapatite and magnetite to the chitosan matrix can noticeably enhance the mechanical properties of the pure chitosan

Collagenous Matrix Supported by A 3D-Printed Scaffold for Osteogenic Differentiation of Dental Pulp Cells

Objective A systematic characterization of hybrid scaffolds, fabricated based on combinatorial additive manufacturing technique and freeze-drying method, is presented as a new platform for osteoblastic differentiation of dental pulp cells (DPCs). Methods The scaffolds were consisted of a collagenous matrix embedded in a 3D-printed beta-tricalcium phosphate (β-TCP) as the mineral phase. The developed construct design was intended to achieve mechanical robustness owing to 3D-printed β-TCP scaffold, and biologically active 3D cell culture matrix pertaining to the Collagen extracellular matrix. The β-TCP precursor formulations were investigated for their flow-ability at various temperatures, which optimized for fabrication of 3D printed scaffolds with interconnected porosity. The hybrid constructs were characterized by 3D laser scanning microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and compressive strength testing. Results The in vitro characterization of scaffolds revealed that the hybrid β-TCP/Collagen constructs offer superior DPCs proliferation and alkaline phosphatase (ALP) activity compared to the 3D-printed β-TCP scaffold over three weeks. Moreover, it was found that the incorporation of TCP into the Collagen matrix improves the ALP activity. Significance The presented results converge to suggest the developed 3D-printed β-TCP/Collagen hybrid constructs as a new platform for osteoblastic differentiation of DPCs for craniomaxillofacial bone regeneration

Porous magnesium-based scaffolds for tissue engineering.

Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail

Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma

Regional delivery of chimeric antigen receptor (CAR) T cells in glioblastoma represents a rational therapeutic approach as an alternative to intravenous administration to avoid the blood-brain barrier impediment. Here, we developed a fibrin gel that accommodates CAR-T cell loading and promotes their gradual release. Using a model of subtotal glioblastoma resection, we demonstrated that the fibrin-based gel delivery of CAR-T cells within the surgical cavity enables superior antitumor activity compared to CAR-T cells directly inoculated into the tumor resection cavity

From Solvent-Free Microspheres to Bioactive Gradient Scaffolds

A solvent-free microsphere sintering technique was developed to fabricate scaffolds with pore size gradient for tissue engineering applications. Poly(D,L-Lactide) microspheres were fabricated through an emulsification method where TiO2 nanoparticles were employed both as particulate emulsifier in the preparation procedure and as surface modification agent to improve bioactivity of the scaffolds. A fine-tunable pore size gradient was achieved with a pore volume of 30±2.6%. SEM, EDX, XRD and FTIR analyses all confirmed the formation of bone-like apatite at the 14th day of immersion in Simulated Body Fluid (SBF) implying the ability of our scaffolds to bond to living bone tissue. In vitro examination of the scaffolds showed progressive activity of the osteoblasts on the scaffold with evidence of increase in its mineral content. The bioactive scaffold developed in this study has the potential to be used as a suitable biomaterial for bone tissue engineering and hard tissue regeneration

Surface stiffening and enhanced photoluminescence of ion implanted cellulose - polyvinyl alcohol - silica composite

Novel Cellulose (Cel) reinforced polyvinyl alcohol (PVA)-Silica (Si) composite which has good stability and in vitro degradation was prepared by lyophilization technique and implanted using N3+ ions of energy 24 keV in the fluences of 1 x 10(15), 5 x 10(15) and 1 x 10(16) ions/cm(2). SEM analysis revealed the formation of microstructures, and improved the surface roughness on ion implantation. In addition to these structural changes, the implantation significantly modified the luminescent, thermal and mechanical properties of the samples. The elastic modulus of the implanted samples has increased by about 50 times compared to the pristine which confirms that the stiffness of the sample surface has increased remarkably on ion implantation. The photoluminescence of the native cellulose has improved greatly due to defect site, dangling bonds and hydrogen passivation. Electric conductivity of the ion implanted samples was improved by about 25%. Hence, low energy ion implantation tunes the mechanical property, surface roughness and further induces the formation of nano structures. MG63 cells seeded onto the scaffolds reveals that with the increase in implantation fluence, the cell attachment, viability and proliferation have improved greatly compared to pristine. The enhancement of cell growth of about 59% was observed in the implanted samples compared to pristine. These properties will enable the scaffolds to be ideal for bone tissue engineering and imaging applications.G.M.S. acknowledges CSIR, India (Grant no: 09/468 (0474)/2013-EMR-I) and S.N.K. thanks the award of Erasmus-Mundus Svaagata for providing financial support to carry out this research. G.M.S., N.S. and S.N.K. acknowledge the support of UGC National facility for characterization facility. J.A.G.T. acknowledges the support of the Spanish Ministry of Economy and Competitiveness (MINECO) through the project DPI2015-65401-C3-2-R (including the FEDER financial support). CIBER-BBN, Spain is an initiative funded by the VI National R&D Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. AFM was conducted by the microscopy service of the UPV, whose advice was greatly appreciated.Shanthini, GM.; Sakthivel, N.; Menon, R.; Nabhiraj, PY.; Gómez-Tejedor, JA.; Meseguer Dueñas, JM.; Gómez Ribelles, JL.... (2016). Surface stiffening and enhanced photoluminescence of ion implanted cellulose - polyvinyl alcohol - silica composite. Carbohydrate Polymers. 153:619-630. https://doi.org/10.1016/j.carbpol.2016.08.016S61963015

Doctor of Philosophy

dissertationAdvances in the synthesis and characterization of engineered silica nanoparticles (SNPs) are not matched by careful assessment of their effects on biological systems, environmental health, and safety. Better understanding of how silica nanoparticles interact with biological fluids and cells is required to predict safety, mechanism of action, dissolution, clearance, and possible adverse effects. In this dissertation the impact of physicochemical properties of SNPs such as size, porosity, density, and surface functionality on cellular toxicity and genomic response was explored on RAW 264.7 macrophages. Size-dependent cytotoxicity was observed. Mesoporous SNPs showed higher LC50 of 223.6±15.6 compared to the similar size nonporous SNPs with LC50 of 33.7±0.6. The observed lower cell association and toxicity of mesoporous particles is probably related to the lower density of silanol groups per square nm on surface. In addition, decreased sedimentation, cell uptake, and toxicity for lower density particles with rattle structure and under flow conditions was observe compared to nonporous particles. The influence of size, porosity, and surface functionality of SNPs on early response of RAW 264.7 macrophages at sub-toxic doses revealed no significant gene expression alteration for nonporous SNPs at 4 h incubation time, however, mesoporous SNPs induced genomic response associated with lysosomal activity. The global gene expression analysis of mesoporous and nonporous nanoparticles with similar diameters of approximately 500 nm showed time- and dose-dependent gene expression response of macrophages as a function of porosity of SNPs