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Development of an ultrasound triggered, thermally responsive hydrogel as an on-demand delivery system for bone repair

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thesis
posted on 21.10.2020, 10:03 by Badriah Ali
Bones can physiologically regenerate themselves. In the case of non-union
fractures and certain pathological conditions, however, regeneration is
suboptimal, too slow, or does not occur. The clinical ‘gold standard’,
autografting, can result in numerous complications including infection, chronic
pain and donor site morbidity. Current commercial bone graft substitutes have
shown limited success and an effective ‘off-the-shelf’ solution is required. The
objective of this study was to develop an ultrasonic-thermally responsive
hydrogel for bone regeneration and to investigate its potential for on-demand
delivery of therapeutic agents in response to ultrasound. Thermo-responsive
hydrogels demonstrate low ultrasonic adsorption properties, which limits their
application as on-demand delivery systems. Calcium phosphates (CaP) have
osteogenic properties and thus can stimulate new bone formation. In addition,
they have high ultrasonic absorption coefficients and thus the potential to act
as solid-phase sonosensitisers within hydrogel systems. This study
hypothesised that the incorporation of hydroxyapatite (HA) particles into an
alginate-based thermo-responsive hydrogel, has the potential to augment the
ultrasound sensitivity of the hydrogel and trigger controlled therapeutic
release to the target tissue, while still demonstrating the necessary
thermoresponsive, rheological and injectability requirements for minimally
invasive application.
Poly(N-isopropylacrylamide) (PNIPAAm) alginate hydrogels were fabricated
and varying quantities (1, 3, 5, and 7 wt %/vol) of HA were incorporated.
Rheological characterisation showed the hydrogel elasticity was lowest for the
1% HA group and increased with increasing HA concentration. The
polymerisation temperature increased following the addition of HA but
remained less than 36.8 ºC for all groups. All hydrogels were shown to be
highly injectable with the maximum force required for injection remaining
below 6.5 N. The release dynamics of three molecules, sodium fluorescein
(NaF) dye, bovine serum albumin (BSA), and bone morphogenetic protein 2
(BMP-2), following the application of a standard ultrasound regime were
explored. Release in response to ultrasound was significantly enhanced in the
HA containing hydrogels, demonstrating that HA effectively increases
sonosensitisation within the hydrogel. Together these results demonstrate that
the ultrasonic-thermally-responsive hydrogels developed here are promising
hydrogels capable of on-demand delivery of therapeutic agents for bone
regeneration.

History

First Supervisor

Dr. Tanya Levingstone

Second Supervisor

Dr. Cathal Kearney

Third Supervisor

Prof. Nicholas Dunne

Comments

A thesis submitted for the degree of Master of Science by Research from the Royal College of Surgeons in Ireland in 2019.

Published Citation

Ali Badriah F M A. Development of an ultrasound triggered, thermally responsive hydrogel as an on-demand delivery system for bone repair [MSc Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.

Degree Name

Master of Science (MSc): Research

Date of award

30/11/2019

Programme

  • Master of Science (MSc): Research

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