While the benefits of both hydrogels and drug delivery to enhance wound healing have been demonstrated, the highly hydrophilic nature of hydrogels creates challenges with respect to the effective ...loading and delivery of hydrophobic drugs beneficial to wound healing. Herein, we utilize pressurized gas expanded liquid (PGX) technology to produce very high surface area (~200 m2/g) alginate scaffolds and describe a method for loading the scaffolds with ibuprofen (via adsorptive precipitation) and crosslinking them (via calcium chelation) to create a hydrogel suitable for wound treatment and hydrophobic drug delivery. The high surface area of the PGX-processed alginate scaffold facilitates >8 wt% loading of ibuprofen into the scaffold and controlled in vitro ibuprofen release over 12–24 h. In vivo burn wound healing assays demonstrate significantly accelerated healing with ibuprofen-loaded PGX-alginate/calcium scaffolds relative to both hydrogel-only and untreated controls, demonstrating the combined benefits of ibuprofen delivery to suppress inflammation as well as the capacity of the PGX-alginate/calcium hydrogel to maintain wound hydration and facilitate continuous calcium release to the wound. The use of PGX technology to produce highly porous scaffolds with increased surface areas, followed by adsorptive precipitation of a hydrophobic drug onto the scaffolds, offers a highly scalable method of creating medicated wound dressings with high drug loadings.
While medicated hydrogel-based wound dressings offer clear advantages in accelerating wound healing, the inherent incompatibility between conventional hydrogels and many poorly water-soluble drugs of relevance in wound healing remains a challenge. Herein, we leveraged supercritical fluids-based strategies to both process and subsequently impregnate alginate, followed by post-crosslinking to form a hydrogel, to create a very high surface area alginate hydrogel scaffold loaded with high hydrophobic drug contents (here, >8 wt% ibuprofen) without the need for any pore-forming additives. The impregnated scaffolds significantly accelerated burn wound healing while also promoting regeneration of the native skin morphology. We anticipate this approach can be leveraged to load clinically-relevant and highly bioavailable dosages of hydrophobic drugs in hydrogels for a broad range of potential applications.
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The physicochemical properties of injectable hydrogels are typically modified by altering the chemistry of the precursor polymer and/or the amount or type of cross-linker, both of which can lead to ...hydrogels with altered mechanics, swelling, degradation, and other key physical properties. Herein, we describe an alternative approach to tune the properties of injectable hydrogels (here, based on hydrazone cross-linked poly(oligoethylene glycol methacrylate), or POEGMA) by altering the architecture of the precursor polymers through branching. Hydrogels prepared using highly branched precursor polymers had nearly identical chemical compositions but exhibited markedly different physical properties relative to linear precursor hydrogels on which we have previously reported. Specifically, increasing the degree of branching resulted in increased degradation time and stiffness but decreased gelation time and gel swelling. The mechanical properties of highly branched hydrogels are relatively insensitive to the mass concentration of precursor polymer used to prepare the gels, in contrast to hydrogels prepared with linear precursors; furthermore, gels prepared from only highly branched precursors exhibit substantially prolonged degradation times compared to all-linear or linear–highly branched hydrogels. Overall, introducing branching in the precursor polymers is demonstrated to provide an alternate strategy to tune injectable hydrogel properties while decoupling otherwise coupled properties (e.g., polymer concentration and mechanics).
Significant challenges remain associated with forming scalable macroporous materials with high interconnectivity without requiring the use of substances that may cause negative effects in the end use ...of the material. In this light, pressurized gas expanded liquid (PGX) technology, a processing technique that uses ethanol and carbon dioxide to create high surface area morphologies in carbohydrate material, offers an attractive alternative. Through the chemical stabilization of these morphologies via crosslinking, the carbohydrate scaffolds can be used in multiple applications including the promotion of cell growth in tissue engineering applications, improvement in wound healing through moisture retention and delivery of biotherapeutics, and creation of interconnected internal morphologies in hard polymers for bioseparations and bone scaffolding applications by way of templating. ;
This thesis investigates these potential applications of PGX-processed materials. First, the effects of the morphology of PGX-processed chitosan crosslinked with varying amounts of genipin (which affect both the gel mechanics and the adhesiveness of the gel) are investigated on the proliferation and morphology of muscle cells. Second, highly interconnected alginate networks created through PGX-processing were impregnated with ibuprofen, ionically crosslinked and evaluated for their use as a burn wound dressing in vivo, with the gels demonstrated to maintain moisture and deliver an anti-inflammatory drug to suppress scarring during wound healing. Finally, alginate networks were used as sacrificial scaffolds in the creation of an interconnected internal morphology within a hard polymer shell for applications requiring both high interconnectivity and high mechanical integrity, such as bone scaffolding and bioseparations. ;
In conclusion, this work shows the promise of post-crosslinked PGX-processed carbohydrates in tissue engineering, wound healing and bioseparations.
Thesis
Master of Applied Science (MASc)
In recent years, many studies have reported substantial populations of large galaxies with low surface brightness in local galaxy clusters. Various theories that aim to explain the presence of such ...ultra-diffuse galaxies (UDGs) have since been proposed. A key question that will help to distinguish between models is whether UDGs have counterparts in host haloes with lower masses, and if so, what their abundance as a function of halo mass is. We here extend our previous study of UDGs in galaxy clusters to galaxy groups. We measure the abundance of UDGs in 325 spectroscopically selected groups from the Galaxy And Mass Assembly (GAMA) survey. We make use of the overlapping imaging from the ESO Kilo-Degree Survey (KiDS), from which we can identify galaxies with mean surface brightnesses within their effective radii down to ~25.5 mag arcsec
-2
in the
r
band. We are able to measure a significant overdensity of UDGs (with sizes
r
eff
≥ 1.5 kpc) in galaxy groups down to
M
200
= 10
12
M
⊙
, a regime where approximately only one in ten groups contains a UDG that we can detect. We combine measurements of the abundance of UDGs in haloes that cover three orders of magnitude in halo mass, finding that their numbers scale quite steeply with halo mass:
N
UDG
(
R
<
R
200
) ∝
M
200
1.11±0.07
. To better interpret this, we also measure the mass-richness relation for brighter galaxies down to
M
r
*
+ 2.5 in the same GAMA groups, and find a much shallower relation of
N
Bright
(
R
<
R
200
) ∝
M
200
0.78±0.05
. This shows that compared to bright galaxies, UDGs are relatively more abundant in massive clusters than in groups. We discuss the implications, but it is still unclear whether this difference is related to a higher destruction rate of UDGs in groups or if massive haloes have a positive effect on UDG formation.
In recent years, many studies have reported substantial populations of large galaxies with low surface brightness in local galaxy clusters. Various theories that aim to explain the presence of such ...ultra-diffuse galaxies (UDGs) have since been proposed. A key question that will help to distinguish between models is whether UDGs have counterparts in host haloes with lower masses, and if so, what their abundance as a function of halo mass is. We here extend our previous study of UDGs in galaxy clusters to galaxy groups. We measure the abundance of UDGs in 325 spectroscopically selected groups from the Galaxy And Mass Assembly (GAMA) survey. We make use of the overlapping imaging from the ESO Kilo-Degree Survey (KiDS), from which we can identify galaxies with mean surface brightnesses within their effective radii down to ~25.5 mag arcsec-2 in the r band. We are able to measure a significant overdensity of UDGs (with sizes reff ≥ 1.5 kpc) in galaxy groups down to M200 = 1012 M⊙, a regime where approximately only one in ten groups contains a UDG that we can detect. We combine measurements of the abundance of UDGs in haloes that cover three orders of magnitude in halo mass, finding that their numbers scale quite steeply with halo mass: NUDG(R < R200) ∝ M2001.11±0.07. To better interpret this, we also measure the mass-richness relation for brighter galaxies down to Mr* + 2.5 in the same GAMA groups, and find a much shallower relation of NBright(R < R200) ∝ M2000.78±0.05. This shows that compared to bright galaxies, UDGs are relatively more abundant in massive clusters than in groups. We discuss the implications, but it is still unclear whether this difference is related to a higher destruction rate of UDGs in groups or if massive haloes have a positive effect on UDG formation.
In recent years, multiple studies have reported substantial populations of large, low-surface-brightness galaxies in local galaxy clusters. Various theories that aim to explain the presence of such ...ultra-diffuse galaxies (UDGs) have since been proposed. A key question that will help to differentiate between models is whether UDGs have counterparts in lower-mass host haloes, and what their abundance as a function of halo mass is. In this study we extend our previous study of UDGs in galaxy clusters to galaxy groups. We measure the abundance of UDGs in 325 spectroscopically-selected groups from the Galaxy And Mass Assembly (GAMA) survey. We make use of the overlapping imaging from the ESO Kilo-Degree Survey (KiDS), from which we can identify galaxies with mean surface brightnesses within their effective radii down to ~25.5 mag arcsec\(^{-2}\) in the r-band. We are able to measure a significant overdensity of UDGs (with sizes r_eff > 1.5 kpc) in galaxy groups down to M200=10^12 Msun, a regime where approximately only 1 in 10 groups contains a UDG that we can detect. We combine measurements of the abundance of UDGs in haloes that cover three orders of magnitude in halo mass, finding that their numbers scale quite steeply with halo mass; N_UDG (R<R200) \(\propto\) M200^(1.11+/-0.07). To better interpret this, we also measure the mass-richness relation for brighter galaxies down to \(M^*_r\)+2.5 in the same GAMA groups, and find a much shallower relation of N_Bright (R<R200) \(\propto\) M200^(0.78+/-0.05). This shows that UDGs are relatively more abundant, compared to bright galaxies, in massive clusters than in groups. We discuss implications, but whether this difference is related to a higher destruction rate of UDGs in groups, or whether massive haloes have a positive effect on their formation, is not yet clear.
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