Ultrasoft, highly deformable microgels

Bachman, Haylee; Brown, Ashley; Clarke, Kimberly C.; Dhada, Kabir S.; Douglas, Alison; Hansen, Caroline E.; Herman, Emily S.; Hyatt, John S.; Kodlekere, Purva; Meng, Zhiyong; Saxena, Shalini; Spears, Mark W.; Welsch, Nicole; Lyon, L. Andrew

doi:10.1039/c5sm00047e

Cited by 91 publications

(104 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microgel mechanics are easily modulated through alterations in the degree of intra-particle crosslinking. In particular, recent reports have demonstrated that microgel deformability can be modulated through crosslinking 5 . Interestingly, for many biomedical applications, particle deformability directly influences bio-functionality.…”

Section: Introductionmentioning

confidence: 99%

Study of Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM) Microgel Particle Induced Deformations of Tissue-Mimicking Phantom by Ultrasound Stimulation

Joshi¹,

Nandi

Chester

et al. 2018

Langmuir

Self Cite

View full text Add to dashboard Cite

Poly (N-isopropylacrilamide) (pNIPAm) microgels (microgels) are colloidal particles that have been used extensively for biomedical applications. Typically, these particles are synthesized in the presence of an exogenous cross-linker, such as N, N′-Methylenebis (acrylamide) (BIS); however, recent studies have demonstrated that pNIPAm microgels can be synthesized in the absence of an exogenous crosslinker, resulting in the formation of ultra-low crosslinked (ULC) particles, which are highly deformable. Microgel deformability has been linked in certain cases to enhanced bioactivity when ULC microgels are used for the creation of biomimetic particles. We hypothesized that ultrasound stimulation of microgels would enhance particle deformation and that the degree of enhancement would negatively correlate with the degree of particle crosslinking. Here, we demonstrate in tissue-mimicking phantoms that using ultrasound insonification causes deformations of ULC microgel particles. Furthermore, the amount of deformation depends on the ultrasound excitation frequency and amplitude, and on the concentration of ULC microgel particles. We observed that the amplitude of deformation increases with increasing ULC microgel particle concentration up to 2.5 mg / 100 ml, but concentrations higher than 2.5 mg / 100 ml result in reduced amount of deformation. In addition, we observed that the amplitude of deformation was significantly higher at 1 MHz insonification frequency. We also report that increasing the degree of microgel crosslinking reduces the magnitude of the deformation and increases the optimal concentration required to achieve the largest amount of deformation. Stimulated ULC microgel particle deformation has numerous potential biomedical applications, including enhancement of localized drug delivery and biomimetic activity. These results demonstrate the potential of ultrasound stimulation for such applications.

show abstract

Section: Introductionmentioning

confidence: 99%

Study of Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM) Microgel Particle Induced Deformations of Tissue-Mimicking Phantom by Ultrasound Stimulation

Joshi¹,

Nandi

Chester

et al. 2018

Langmuir

Self Cite

View full text Add to dashboard Cite

show abstract

“…ULC μgels are composed of poly(N-isopropylacrylamide) (pNIPAM) copolymerized with acrylic acid (AAc) and synthesized in the absence of exogenous cross-linker. Cross-linking and branching of the polymer chains forming these unique particles occurs via rare parasitic chain transfer reactions (16) rendering extremely deformable particles (17). When deposited on a glass surface, as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The long migration distances also suggest that the cells rather exploit the long-time viscous behavior of the μgel suspension. of 2 mol % N,N'-methylene(bisacrylamide) (BIS) (16)(17)(18)22). Purified μgels were labeled with AlexaFluor dyes and lyophilized for future use.…”

Section: Methodsmentioning

confidence: 99%

Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers

Douglas

Fragkopoulos

Gaines

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

In regenerative medicine, natural protein-based polymers offer enhanced endogenous bioactivity and potential for seamless integration with tissue, yet form weak hydrogels that lack the physical robustness required for surgical manipulation, making them difficult to apply in practice. The use of higher concentrations of protein, exogenous cross-linkers, and blending synthetic polymers has all been applied to form more mechanically robust networks. Each relies on generating a smaller network mesh size, which increases the elastic modulus and robustness, but critically inhibits cell spreading and migration, hampering tissue regeneration. Here we report two unique observations; first, that colloidal suspensions, at sufficiently high volume fraction (ϕ), dynamically assemble into a fully percolated 3D network within high-concentration protein polymers. Second, cells appear capable of leveraging these unique domains for highly efficient cell migration throughout the composite construct. In contrast to porogens, the particles in our system remain embedded within the bulk polymer, creating a network of particle-filled tunnels. Whereas this would normally physically restrict cell motility, when the particulate network is created using ultralow cross-linked microgels, the colloidal suspension displays viscous behavior on the same timescale as cell spreading and migration and thus enables efficient cell infiltration of the construct through the colloidal-filled tunnels.fibrin | microgels | colloidal assemblies | porosity | cell migration D ecoupling stiffness, pore size, and cell infiltration is a critical hurdle in biomaterials design and has been previously addressed in synthetic hydrogels by enabling cell-mediated degradation via protease-specific peptide cross-linkers (1-4). However, even in these highly engineered systems, compared with native extracellular matrices (ECMs), the mesh size remains a critical limiting factor in host integration; this is because cells are incapable of nonproteolytic, i.e., degradation-independent, migration through such small mesh sizes (5), as illustrated in Fig. 1A.Protein-based biomaterials derived from native ECM represent an attractive alternative to synthetic hydrogels, offering significant benefits through their enhanced endogenous bioactivity. The native ECM and its derivatives act as growth factor/cytokine depots, thus providing a multivalent endogenous binding site for growth factor delivery (6). A classic example of this type of biomaterial is fibrin, the endogenous provisional matrix formed at sites of vascular injury as a result of blood coagulation (7,8). Clinically, to reach desirable mechanical properties for sealing tissues/wounds, fibrin is used at supraphysiological concentrations typically containing ∼10× more fibrinogen than physiological concentrations (9-12). When used at these artificially high concentrations, the characteristic mesh size of the network is unfortunately similar to that of synthetic PEG polymers, which is on the order of tens of nanometers, making i...

show abstract

“…[21] Due to the low connectivity of polymer chains within the formed network, cross-linker-free pNiPAm microgels show high levels of deformability and spreading. [23] The mechanical behavior of soft hydrogels has become an important research area for various applications including biomaterial design. [24] For example, Merkel et al .…”

Section: Introductionmentioning

confidence: 99%

Oligo(ethylene glycol)-sidechain microgels prepared in absence of cross-linking agent: Polymerization, characterization and variation of particle deformability

Welsch

Lyon

2017

PLoS ONE

Self Cite

View full text Add to dashboard Cite

We present a systematic study of self-cross-linked microgels formed by precipitation polymerization of oligo ethylene glycol methacrylates. The cross-linking density of these microgels and, thus, the network flexibility can be easily tuned through the modulation of the reaction temperature during polymerization. Microgels prepared in absence of any difunctional monomer, i.e. cross-linker, show enhanced deformability and particle spreading on solid surfaces as compared to microgels cross-linked with varying amounts of poly(ethylene glycol diacrylate) (PEG-DA) in addition to self-crosslinking. Particles prepared at low reaction temperatures exhibit the highest degree of spreading due to the lightly cross-linked and flexible polymer network. Moreover, AFM force spectroscopy studies suggest that cross-linker-free microgels constitute of a more homogeneous polymer network than PEG-DA cross-linked particles and have elastic moduli at the particle apex that are ~5 times smaller than the moduli of 5 mol-% PEG-DA cross-linked microgels. Resistive pulse sensing experiments demonstrate that microgels prepared at 75 and 80°C without PEG-DA are able to deform significantly to pass through nanopores that are smaller than the microgel size. Additionally, we found that polymer network flexibility of microgels is a useful tool to control the formation of particle dewetting patterns. This offers a promising new avenue for build-up of 2D self-assembled particle structures with patterned chemical and mechanical properties.

show abstract

Ultrasoft, highly deformable microgels

Cited by 91 publications

References 29 publications

Study of Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM) Microgel Particle Induced Deformations of Tissue-Mimicking Phantom by Ultrasound Stimulation

Study of Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM) Microgel Particle Induced Deformations of Tissue-Mimicking Phantom by Ultrasound Stimulation

Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers

Oligo(ethylene glycol)-sidechain microgels prepared in absence of cross-linking agent: Polymerization, characterization and variation of particle deformability

Contact Info

Product

Resources

About