Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications

Adriana Matamoros-Veloza; Kazi M.Zakir Hossain; Brigitte E. Scammell; Ifty Ahmed; Richard Hall; Nikil Kapur

doi:10.1016/j.jmbbm.2019.103489

Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications

Adriana Matamoros-Veloza^*, Kazi M.Zakir Hossain, Brigitte E. Scammell, Ifty Ahmed, Richard Hall, Nikil Kapur

^*Corresponding author for this work

Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Current trends in regenerative medicine treatments for bone repair applications focus on cell-based therapies. These aim to deliver the treatment via a minimally invasive injection to reduce patient trauma and to improve efficacy. This paper describes the injectability of porous calcium phosphate glass microspheres to be used for bone repair based on their formulation, rheology and flow behavior. The use of excipients (xanthan gum, methyl cellulose and carboxyl methyl cellulose) were investigated to improve flow performance. Based on our results, the flow characteristics of the glass microsphere pastes vary according to particle size, surface area, and solid to liquid ratio, as well as the concentration of viscosity modifiers used. The optimal flow characteristics of calcium phosphate glass microsphere pastes was found to contain 40 mg/mL of xanthan gum which increased viscosity whilst providing elastic properties (∼29,000 Pa) at shear rates that mirror the injection process and the resting period post injection, preventing the glass microspheres from both damage and dispersion. It was established that a base formulation must contain 1 g of glass microspheres (60–125 μm in size) per 1 mL of cell culture media, or 0.48 g of glass microspheres of sizes between 125 and 200 μm. Furthermore, the glass microsphere formulations with xanthan gum were readily injectable via a syringe-needle system (3–20 mL, 18G and 14G needles), and have the potential to be utilized as a cell (or other biologics) delivery vehicle for bone regeneration applications.

Original language	English
Article number	103489
Journal	Journal of the Mechanical Behavior of Biomedical Materials
Volume	102
DOIs	https://doi.org/10.1016/j.jmbbm.2019.103489
Publication status	Published - Feb 2020

Bibliographical note

Funding Information:
This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001 ). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies.

Funding Information:
This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies.

Publisher Copyright:
© 2019

Keywords

Bone regeneration
Injectable paste
Minimal invasive technology
Osteoporosis
Porous microspheres

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering
Mechanics of Materials

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10.1016/j.jmbbm.2019.103489

Cite this

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title = "Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications",

abstract = "Current trends in regenerative medicine treatments for bone repair applications focus on cell-based therapies. These aim to deliver the treatment via a minimally invasive injection to reduce patient trauma and to improve efficacy. This paper describes the injectability of porous calcium phosphate glass microspheres to be used for bone repair based on their formulation, rheology and flow behavior. The use of excipients (xanthan gum, methyl cellulose and carboxyl methyl cellulose) were investigated to improve flow performance. Based on our results, the flow characteristics of the glass microsphere pastes vary according to particle size, surface area, and solid to liquid ratio, as well as the concentration of viscosity modifiers used. The optimal flow characteristics of calcium phosphate glass microsphere pastes was found to contain 40 mg/mL of xanthan gum which increased viscosity whilst providing elastic properties (∼29,000 Pa) at shear rates that mirror the injection process and the resting period post injection, preventing the glass microspheres from both damage and dispersion. It was established that a base formulation must contain 1 g of glass microspheres (60–125 μm in size) per 1 mL of cell culture media, or 0.48 g of glass microspheres of sizes between 125 and 200 μm. Furthermore, the glass microsphere formulations with xanthan gum were readily injectable via a syringe-needle system (3–20 mL, 18G and 14G needles), and have the potential to be utilized as a cell (or other biologics) delivery vehicle for bone regeneration applications.",

keywords = "Bone regeneration, Injectable paste, Minimal invasive technology, Osteoporosis, Porous microspheres",

author = "Adriana Matamoros-Veloza and Hossain, {Kazi M.Zakir} and Scammell, {Brigitte E.} and Ifty Ahmed and Richard Hall and Nikil Kapur",

note = "Funding Information: This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001 ). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies. Funding Information: This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies. Publisher Copyright: {\textcopyright} 2019",

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AU - Scammell, Brigitte E.

AU - Ahmed, Ifty

AU - Hall, Richard

AU - Kapur, Nikil

N1 - Funding Information: This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001 ). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies. Funding Information: This paper summarizes independent research funded by the National Institute for Health Research, United Kingdom (NIHR) under its i4i Challenge Award Programme (Grant Reference Number: II-C3-0714-20001). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors would also like to acknowledge Tony Wiese and for his support during force measurements. Also, we would like to thank Ceramisys Limited (UK) for their kind contribution to gamma sterilization studies. Publisher Copyright: © 2019

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Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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