Uresha Patel

Dr Emma Barney Dr Andrew Kennedy, Dr Alex Hannon (ISIS) Dr Ifty Ahmed

Manufacture and Structural Characterisation of Resorbable Phosphate-Based Glass Microspheres for Biomedical Applications

Acknowledgment: The authors would like to acknowledge funding received from the Science and Technology Facilities Council (STFC ref. no. ST/L502583/1 )

A world wide ageing population is placing increasing demands on health care systems to provide effective treatment for bone related disorders such as osteoporosis.

As such, there is a major on-going shift in emphasis from tissue repair to tissue regeneration as a solution to the ever-growing need for long-term orthopaedic care.

Incorporation of therapeutic ions into phosphate based glasses (PBG) is of growing interest. In particular, addition of strontium has been investigated, since Sr2+ has shown to exert a positive influence on bone remodelling [1].

This study focused on compositional development of PBGs to optimise the therapeutic effect of these glasses, by understanding the dissolution and structure of the glass.

The aim of this study was to manufacture and characterise bulk and porous PBG microspheres for biomedical applications.

Healthy Bone Osteoporotic bone

Growth factors

Stem cells

Drugs

Proteins

Therapeutic ions

These PBG hold the potential of providing a combinatorial effect to aid repair and regeneration of bone

Fig 2.1 3D visualisation of porous microspheres Acknowledgement: Dr Martin Corfield image taken on XRADIA Versa XRM-500 system

Neutron diffraction studies (Figure 3.1) suggest substitution of Ca with Sr does

not significantly change the local environment of modifiers. From the T(r) and ∆T(r) it is possible to estimate the bond length between the modifier oxides.

(a)

(b)

Fig 3.1 Real –space diffraction data for (a) total diffraction pattern of P40 and Sr16, (b) the difference function between P40 and Sr16.

31 P Solid-state NMR spectra (Fig 3.2) (obtained at the EPSRC UK National Solid-state NMR Service Durham) complimented the diffraction data as the Q1 and Q2 species were consistent for all compositions at 50% ±1.

Fig 3.2 Solid-state 31P NMR spectra were obtained at the EPSRC UK National Solid-state NMR Service at Durham.

Fig 3.3 Average mass loss (%) of each sample over a 35 day period in deionised water showed no sig. difference between Sr compositions.

[1] Kyllonen L et al. Acta Biomaterialia. 11: 412-434, 2011 [2] Nielsen S, Bone. 35(3): 583-588, 2004

Acknowledgment: The authors would like to acknowledge funding received from the Science and Technology Facilities Council (STFC ref. no. ST/L502583/1 )

When comparing properties of Ca2+ and Sr2+ in terms of ionic size and charge, it was expected that substitution of calcium oxide for strontium oxide would play a similar role. Both elements follow a similar physiological pathway and are primarily concentrated in the bone [2].

Analysis showed it was possible to substitute Sr2+ for Ca2+ without drastically affecting the network structure of the glass as well as having little effect on the degradation between compositions, suggesting it may be possible to release a controlled concentration of Sr ions during degradation.

This study has also shown that both bulk and porous microspheres can be manufactured in mass with a certain degree of control over porosity. Furthermore ,recent studies have shown interconnectivity of pores can be enhanced via a post processing method (Fig 4.1).

Porous microspheres would be loaded with biological components such as stem cells. Their spherical morphology enables these microspheres to flow more easily compared to irregular shaped particles. Ideally such treatments would be administrated on a day case basis via a minimally invasive route. Ultimately this project aims to develop a prophylactic treatment for the prevention of fragility fractures.

Fig 4.1 SEM showing interconnected pores

A flame spheroidisation technique was used to create bulk microspheres in the size range of 63-125µm.

Glass system investigated (mol%):

P2O5(40) CaO(16-x) Na2O(20) MgO(24) SrO(x)

where x = 0, 4, 8, 12, 16

The PBG composition was further developed to

optimise the therapeutic effect of these glasses, by understanding the dissolution and structure of the glass.

Fig 1.1 SEM showing yield of (a) bulk and (b) porous microspheres

(a) (b)