Publications

@article{Molinar-Diaz2024-wm,

title = {Development of resorbable phosphate-based glass microspheres as  MRI contrast media agents},

author = {Jes\'{u}s Molinar-D\'{i}az and Andi Arjuna and Nichola Abrehart and Alison McLellan and Roy Harris and Md Towhidul Islam and Ahlam Alzaidi and Chris R Bradley and Charlotte Gidman and Malcolm J W Prior and Jeremy Titman and Nicholas P Blockley and Peter Harvey and Luca Marciani and Ifty Ahmed},

doi = {10.3390/molecules29184296},

year  = {2024},

date = {2024-09-01},

urldate = {2024-09-01},

journal = {Molecules},

volume = {29},

number = {18},

pages = {4296},

publisher = {MDPI AG},

abstract = {In this research, resorbable phosphate-based glass (PBG) 

 compositions were developed using varying modifier oxides 

 including iron (Fe2O3), copper (CuO), and manganese (MnO2), and 

 then processed via a rapid single-stage flame spheroidisation 

 process to manufacture dense (i.e., solid) and highly porous 

 microspheres. Solid (63-200 µm) and porous (100-200 µm) 

 microspheres were produced and characterised via SEM, XRD, and 

 EDX to investigate their surface topography, structural 

 properties, and elemental distribution. Complementary NMR 

 investigations revealed the formation of Q2, Q1, and Q0 

 phosphate species within the porous and solid microspheres, and 

 degradation studies performed to evaluate mass loss, particle 

 size, and pH changes over 28 days showed no significant 

 differences among the microspheres (63-71 µm) investigated. The 

 microspheres produced were then investigated using clinical (1.5 

 T) and preclinical (7 T) MRI systems to determine the R1 and R2 

 relaxation rates. Among the compositions investigated, 

 manganese-based porous and solid microspheres revealed enhanced 

 levels of R2 (9.7-10.5 s-1 for 1.5 T; 17.1-18.9 s-1 for 7 T) and 

 R1 (3.4-3.9 s-1 for 1.5 T; 2.2-2.3 s-1 for 7 T) when compared to 

 the copper and iron-based microsphere samples. This was 

 suggested to be due to paramagnetic ions present in the Mn-based 

 microspheres. It is also suggested that the porosity in the 

 resorbable PBG porous microspheres could be further explored for 

 loading with drugs or other biologics. This would further 

 advance these materials as MRI theranostic agents and generate 

 new opportunities for MRI contrast-enhancement oral-delivery 

 applications.},

keywords = {Magnetic Resonance Imaging, oral contrast agents, phosphate-based glasses, porous microspheres, resorbable   materials},

pubstate = {published},

tppubtype = {article}

}

@article{Molinar-Diaz2023-kp,

title = {Optimisation of the flame spheroidisation process for the rapid 

 manufacture of Fe3O4-based porous and dense microspheres},

author = {Jes\'{u}s Molinar-D\'{i}az and John Luke Woodliffe and Elisabeth Steer and Nicola A Morley and Paul D Brown and Ifty Ahmed},

year  = {2023},

date = {2023-03-01},

journal = {Molecules},

volume = {28},

number = {6},

abstract = {The rapid, single-stage, flame-spheroidisation process, as 

 applied to varying Fe3O4:CaCO3 powder combinations, provides for 

 the rapid production of a mixture of dense and porous 

 ferromagnetic microspheres with homogeneous composition, high 

 levels of interconnected porosity and microsphere size control. 

 This study describes the production of dense (35-80 µm) and 

 highly porous (125-180 µm) Ca2Fe2O5 ferromagnetic microspheres. 

 Correlated backscattered electron imaging and mineral liberation 

 analysis investigations provide insight into the microsphere 

 formation mechanisms, as a function of Fe3O4/porogen mass ratios 

 and gas flow settings. Optimised conditions for the processing of 

 highly homogeneous Ca2Fe2O5 porous and dense microspheres are 

 identified. Induction heating studies of the materials produced 

 delivered a controlled temperature increase to 43.7 °C, 

 indicating that these flame-spheroidised Ca2Fe2O5 ferromagnetic 

 microspheres could be highly promising candidates for magnetic 

 induced hyperthermia and other biomedical applications.},

keywords = {calcium ferrites, ceramics, flame spheroidisation, magnetic   hyperthermia, magnetic particles, magnetite, porous microspheres},

pubstate = {published},

tppubtype = {article}

}

@article{Islam2022-yy,

title = {Evolution of silicate bioglass particles as porous microspheres 

 with a view towards orthobiologics},

author = {Md Towhidul Islam and Nur Aisyah Nuzulia and Laura Macri-Pellizzeri and Farah Nigar and Yessie W Sari and Ifty Ahmed},

year  = {2022},

date = {2022-03-01},

journal = {J. Biomater. Appl.},

volume = {36},

number = {8},

pages = {1427\textendash1443},

publisher = {SAGE Publications},

abstract = {Although FDA approved and clinically utilised, research on 45S5 

 Bioglass® and S53P4 including other bioactive 

 glasses continues in order to advance their applicability for a 

 range of alternate applications. For example, rendering these 

 particles porous would enable incorporation of varying 

 biological payloads (i.e. cells, drugs and growth factors) and 

 making them spherical would enhance their flow properties 

 enabling delivery to target sites via minimally invasive 

 injection procedures. This paper reports on the manufacture of 

 solid (non-porous; SGMS) and highly porous microspheres (PGMS) 

 with large external pores and fully interconnected porosity from 

 bioactive silicate glass formulations (45S5 and S53P4) via a 

 single stage flame spheroidisation process and their 

 physicochemical properties including in vitro biological 

 response. Morphological and physical characterisation of the 

 SGMS and PGMS revealed interconnected porosity up to 65 $±$ 

 5%. Mass loss studies comparing between SGMS and PGMS revealed 

 1.5 times higher mass loss for the PGMS over 28 days. Also, in 

 vitro bioactivity studies using simulated body fluid (SBF) 

 revealed hydroxyapatite (HA) formation at earlier time point for 

 PGMS compared to their SGMS counterparts (i.e day 1 for PGMS and 

 day 3 for SGMS of 45S5). In addition, HA layers were also formed 

 in cell culture media, with the exception of SGMS of 45S5, which 

 revealed CaP formation with a ratio of 1.52-1.78. Direct cell 

 seeding and indirect cell culture studies (via incubation with 

 microsphere degradation products) revealed mouse 3T3 cells were 

 able to grow and undergo osteogenic differentiation in vitro, 

 confirming cytocompatibility of both 45S5 and S53P4 SGMS and 

 PGMS. More importantly and especially for orthobiologic 

 applications, cells were observed to have migrated within the 

 pores of the PGMS. As such, the PGMS developed from these 

 bioactive silicate glasses are highly promising candidate 

 materials for orthobiologics and alternate applications 

 requiring delivery of biologic payloads.},

keywords = {bioactive glasses, bioactivity, cytocompatibility, mass loss, orthobiologics, osteogenic differentiation, porous microspheres, thermal properties},

pubstate = {published},

tppubtype = {article}

}

@article{Islam2021-qd,

title = {Effect of varying the Mg with Ca content in highly porous 

 phosphate-based glass microspheres},

author = {Md Towhidul Islam and Laura Macri-Pellizzeri and Kazi M Zakir Hossain and Virginie Sottile and Ifty Ahmed},

year  = {2021},

date = {2021-01-01},

journal = {Mater. Sci. Eng. C Mater. Biol. Appl.},

volume = {120},

number = {111668},

pages = {111668},

publisher = {Elsevier BV},

abstract = {This paper reports on the role of phosphate-based glass (PBG) 

 microspheres and their physicochemical properties including in 

 vitro biological response to human mesenchymal stem cells 

 (hMSCs). Solid and porous microspheres were prepared via a flame 

 spheroidisation process. The Mg content in the PBG formulations 

 explored was reduced from 24 to 2 mol% with a subsequent 

 increase in Ca content. A small quantity of TiO2 (1 mol%) was 

 added to the lower Mg-content glass (2 mol%) to avoid 

 crystallisation. Morphological and physical characterisation of 

 porous microspheres revealed interconnected porosity (up to 76 

 $±$ 5 %), average external pore sizes of 55 $±$ 5 μm 

 with surface areas ranging from 0.38 to 0.43 m2 g-1. Degradation 

 and ion release studies conducted compared the solid 

 (non-porous) and porous microspheres and revealed 1.5 to 2.5 

 times higher degradation rate for porous microspheres. Also, in 

 vitro bioactivity studies using simulated body fluid (SBF) 

 revealed Ca/P ratios for porous microspheres of all three glass 

 formulations were between 0.75 and 0.92 which were within the 

 range suggested for precipitated amorphous calcium phosphate. 

 Direct cell seeding and indirect cell culture studies (via 

 incubation with microsphere degradation products) revealed hMSCs 

 were able to grow and undergo osteogenic differentiation in 

 vitro, confirming cytocompatibility of the formulations tested. 

 However, the higher Mg content (24 mol%) porous microsphere 

 showed the most potent osteogenic response and is therefore 

 considered as a promising candidate for bone repair 

 applications.},

keywords = {bioactivity, cytocompatibility, Degradation, Ion release, osteogenic differentiation, porous microspheres, Thermal   properties},

pubstate = {published},

tppubtype = {article}

}