Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

Fabiilli, Mario L.; Wilson, Christopher G.; Padilla, F.; Martín-Saavedra, Francisco M.; Fowlkes, J. Brian; Franceschi, Renny T.

doi:10.1016/j.actbio.2013.03.027

Cited by 69 publications

(69 citation statements)

References 76 publications

(85 reference statements)

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“…Ultrasound (US), in conjunction with sonosensitive particles, has been studied as a means of interacting with active scaffolds to achieve both spatial and temporal control exogenously [27, 28]. US can be applied non-invasively, focused with sub-millimeter precision, and reach deeply located implants.…”

Section: Introductionmentioning

confidence: 99%

“…US can be applied non-invasively, focused with sub-millimeter precision, and reach deeply located implants. US-sensitive hydrogels can be fabricated by doping the scaffold with sonosensitive emulsions or microbubbles, the latter of which are used clinically for contrast enhanced US imaging [27, 29]. Possessing greater stability than microbubbles, sonosensitive emulsions are composed of nano- or micron-sized droplets, contain a liquid perfluorocarbon (PFC) core, and are stabilized by a surfactant shell.…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

et al. 2016

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Spatiotemporally controlled release of growth factors (GFs) is critical for regenerative processes such as angiogenesis. A common strategy is to encapsulate the GF within hydrogels, with release being controlled via diffusion and/or gel degradation (i.e., hydrolysis and/or proteolysis). However, simple encapsulation strategies do not provide spatial or temporal control of GF delivery, especially non-invasive, on-demand controlled release post implantation. We previously demonstrated that fibrin hydrogels, which are widely used in tissue engineering and GF delivery applications, can be doped with perfluorocarbon emulsion, thus yielding an acoustically responsive scaffold (ARS) that can be modulated with focused ultrasound, specifically via a mechanism termed acoustic droplet vaporization. This study investigates the impact of ARS and ultrasound properties on controlled release of a surrogate payload (i.e., fluorescently-labeled dextran) and fibrin degradation in vitro and in vivo. Ultrasound exposure (2.5 MHz, peak rarefactional pressure: 8 MPa, spatial peak time average intensity: 86.4 mW/cm2), generated up to 7.7 and 21.7-fold increases in dextran release from the ARSs in vitro and in vivo, respectively. Ultrasound also induced morphological changes in the ARS. Surprisingly, up to 2.9-fold greater blood vessel density was observed in ARSs compared to fibrin when implanted subcutaneously, even without delivery of pro-angiogenic GFs. The results demonstrate the potential utility of ARSs in generating controlled release for tissue regeneration.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

et al. 2016

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“…119 For instance, fibrin hydrogels doped with microdroplets containing basic fibroblast growth factors (bFGF) could be acoustically activated to release bFGF. 48 Release of bFGFs was five times higher with US application. Also, changes in scaffold mechanical properties caused by the transition of droplets into bubbles could be regulated by varying US intensity.…”

Section: Perfluorocarbon Particlesmentioning

confidence: 95%

“…Also, changes in scaffold mechanical properties caused by the transition of droplets into bubbles could be regulated by varying US intensity. 48 These studies were conducted in vitro , but show the potential of controlling TERM agent release in vivo . This would provide future therapies with control and visualization of therapeutic release and allow treatment customization on a per patient basis.…”

Section: Perfluorocarbon Particlesmentioning

confidence: 99%

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

et al. 2015

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The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

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“…More recently, perfluorocarbon droplets have been shown to lower the acoustic power needed for HIFU-mediated lysis of blood clots relative to HIFU exposure without droplets [15]. Spatiotemporally-controlled ADV-mediated drug release from perfluorocarbon double emulsions has also been shown to regulate the mechanical properties of tissue-engineered scaffolds [16].…”

Section: Introductionmentioning

confidence: 99%

Scavenging dissolved oxygen via acoustic droplet vaporization

Radhakrishnan

Holland

Haworth

2014

The Journal of the Acoustical Society of America

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Acoustic droplet vaporization (ADV) of perfluorocarbon emulsions has been explored for diagnostic and therapeutic applications. Previous studies have demonstrated that vaporization of a liquid droplet results in a gas microbubble with a diameter 5 to 6 times larger than the initial droplet diameter. The expansion factor can increase to a factor of 10 in gassy fluids as a result of air diffusing from the surrounding fluid into the microbubble. This study investigates the potential of this process to serve as an ultrasound-mediated gas scavenging technology. Perfluoropentane droplets diluted in phosphate-buffered saline (PBS) were insonified by a 2 MHz transducer at peak rarefactional pressures lower than and greater than the ADV pressure amplitude threshold in an in vitro flow phantom. The change in dissolved oxygen (DO) of the PBS before and after ADV was measured. A numerical model of gas scavenging, based on conservation of mass and equal partial pressures of gases at equilibrium, was developed. At insonation pressures exceeding the ADV threshold, the DO of air-saturated PBS decreased with increasing insonation pressures, dropping as low as 25% of air saturation within 20 s. The decrease in DO of the PBS during ADV was dependent on the volumetric size distribution of the droplets and the fraction of droplets transitioned during ultrasound exposure. Numerically predicted changes in DO from the model agreed with the experimentally measured DO, indicating that concentration gradients can explain this phenomenon. Using computationally modified droplet size distributions that would be suitable for in vivo applications, the DO of the PBS was found to decrease with increasing concentrations. This study demonstrates that ADV can significantly decrease the DO in an aqueous fluid, which may have direct therapeutic applications and should be considered for ADV-based diagnostic or therapeutic applications.

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Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

Cited by 69 publications

References 76 publications

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

Scavenging dissolved oxygen via acoustic droplet vaporization

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