Steven R Little

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (75)335.85 Total impact

  • Melissa H. Lash, Morgan Fedorchak, Steven R. Little
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    ABSTRACT: Hierarchically ordered porous materials hold promise for enhanced performance in a variety of fields. Specifically, in terms of a hierarchical pore structure (ranging from the nano-micron size regimes) many practical advantages can be derived from having a high surface area and pore volume, as well as providing size selectivity for molecule/particle diffusion and substantial interfacial area. An exceptionally promising technique for the formation of ordered porous materials is the use of colloidal crystal templating, with much attention paid to nano-scale self-assembly. Larger (micron-scale particle) components, however, offer benefits from a mass transfer as well as mechanical strength perspective and often involve easier synthesis of materials, easier yet potentially more sophisticated surface functionality, simpler measurements of the assembly process, and greater control of the interaction strength and selectivity. Despite these advantages, self-assembly at larger scales remains in its infancy. Larger components become more readily arrested in a non-equilibrium configuration (compared to nano-scale counterparts) as these larger systems are less influenced by the underlying thermal effects. This tendency for kinetic arrest limits the translation of nano-scale assembly techniques up to larger component scales. In this work, ultrasonic agitation is explored as a means of allowing large microparticles (18-750m) to overcome kinetic barriers to packing in the creation of close-packed, highly ordered, crystalline structures. Specifically, the relationship between particle packing behavior and energy input is being characterized in terms of crystallinity. Additionally, we have extended this technique for crystal fabrication to create multi-component crystals made from two or more particle sizes. When we combine these "large-particle" assembly techniques with traditional nano-scale colloidal crystallization an exciting opportunity arises to tailor the mechanical and surface properties as well as the pore size of the resulting hierarchically structured materials.
    14 AIChE Annual Meeting; 11/2014
  • Melissa H. Lash, Morgan Fedorchak, Steven R. Little
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    ABSTRACT: Particle-based crystals have been explored as a basis for creating ordered porous materials for applications in molecular electronics, photonics, sensors, and drug delivery. However, much of the research on these crystals has been focused on particles of nano and sub-micron dimensions (so-called colloidal crystals) with limited attention directed towards building blocks with dimensions ranging from tens to hundreds of microns. Larger (particle) components, however, offer many practical benefits ranging from a mass transfer as well as mechanical strength perspective and often involve easier synthesis of materials, easier yet potentially more sophisticated surface functionality, simpler measurements of the assembly process, and greater control of the interaction strength and selectivity. Despite these advantages, self-assembly at larger scales remains in its infancy. Components on the meso- and macro-scales are generally influenced by forces within the system in a different manner than their nano-scale counterparts; the underlying thermal effects in these larger systems typically cannot naturally overcome kinetic barriers generally leading to the components becoming kinetically arrested in non-equilibrium states. In this work, we introduce ultrasonic agitation into a system of large particles (or mixtures of particles) and explore the impact that external agitation at varying input energies has on the packing behavior of both monodispersed microparticle populations as well as mixtures of microparticles. Additionally, we will examine the implications of this work on the resulting mechanical properties of “large particle”-based crystals (both monodisperse and mixed-size). The implications of this work will hopefully lead to a better understanding of the assembly behavior and resulting mechanical properties of “large particle”-based crystals.
    14 AIChE Annual Meeting; 11/2014
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    ABSTRACT: Disease and injury perturb the balance of processes associated with inflammation and tissue remodeling, resulting in positive feedback loops, exacerbation of disease and compromised tissue repair. Conversely, under homeostatic healthy conditions, these processes are tightly regulated through the expansion and/or recruitment of specific cell populations, promoting a balanced steady-state. Better understanding of these regulatory processes and recent advances in biomaterials and biotechnology have prompted strategies to utilize cells for the treatment and prevention of disease through regulation of inflammation and promotion of tissue repair. Herein, we describe how cells that regulate these processes can be increased in prevalence at a site of disease or injury. We review several relevant cell therapy approaches as well as new strategies for directing endogenous regulatory cells capable of promoting environmental homeostasis and even the establishment of a pro-regenerative micro-environment. Collectively, these examples may provide a blueprint for next-generation "medicine" that spurs the body's own cells to action and replaces conventional drugs.
    Annals of Biomedical Engineering 09/2014; · 3.23 Impact Factor
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    ABSTRACT: Inflammatory bone resorption is a hallmark of periodontitis, being Treg and Th2 cells independently associated with disease progression attenuation. In this study, we employed an infection-triggered inflammatory osteolysis model to investigate the mechanisms underlying Treg and Th2 cell migration and impact on disease outcome. A. actinomycetemcomitans-infected C57Bl/6 (WT) mice develop an intense inflammatory reaction and alveolar bone resorption, being Tregs of Th2 cells migration temporally associated with disease progression attenuation. Tregs extracted from the lesions preferentially express CCR4 and CCR8, while Th2 cells express CCR3, CCR4 and CCR8. The absence of CCR5 and CCR8 did not impact Th2 and Tregs migration or disease outcome in a significant manner. CCR4KO mice presented a minor reduction in Th2 in parallel with major impairment of Tregs migration, associated with increased inflammatory bone loss and higher pro-inflammatory and osteoclastogenic cytokines levels. The blockade of the CCR4 ligand CCL22 in WT mice resulted in increased inflammatory bone loss phenotype similarly to CCR4KO strain. Adoptive transfer of CCR4+Tregs to CCR4KO strain revert the increased disease phenotype to WT mice-like levels, being the production of CCL22 in the lesions mandatory for Tregs migration and the consequent bone loss arrest. The local release of exogenous CCL22 provided by PLGA-microparticles promote Tregs migration and disease arrest in the absence of endogenous CCL22 IL-4KO strain, characterized by the lack of endogenous CCL22 production, defective Tregs migration and exacerbated bone loss. In summary, our results demonstrate that the involvement of IL-4/CCL22/CCR4 axis in the migration of Tregs to osteolytic lesions sites, and attenuates development of lesions by inhibiting inflammatory migration and the production of pro-inflammatory and osteoclastogenic mediators. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2014; · 6.04 Impact Factor
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    ABSTRACT: The ability to deliver but hide immunogenic payloads and then reveal them at predetermined times could lead to autonomously boosting vaccine formulations or improved antigen–adjuvant vaccine designs. We used in silico modeling to determine the appropriate formulation and material properties for poly(lactic-co-glycolic) acid (PLGA) microparticles such that they would delay the in vitro “unmasking” of an ovalbumin-alum payload for precise and predetermined intervals. A preferred formulation was then tested in vivo. In vivo T cell proliferation data confirmed the presentation of antigen released through the programmed delayed burst while antibody subclass data demonstrated immunogenicity comparable to that observed with established multiple injection prime-boost regimens.
    J. Mater. Chem. B. 08/2014; 2(37).
  • G P Garlet, C S Sfeir, S R Little
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    ABSTRACT: The disruption of host-microbe homeostasis at the site of periodontal disease is considered a key factor for disease initiation and progress. While the downstream mechanisms responsible for the tissue damage per se are relatively well-known (involving various patterns of immune response operating toward periodontal tissue destruction), we are only beginning to understand the complexity of host-microbe interactions in the periodontal environment. Unfortunately, most of the research has been focused on the disruption of host-microbe homeostasis instead of focusing on the factors responsible for maintaining homeostasis. In this context, regulatory T-cells (Tregs) comprise a CD4+FOXp3 +T-cell subset with a unique ability to regulate other leukocyte functions to avoid excessive immune activation and its pathological consequences. Tregs act as critical determinants of host-microbe homeostasis, as well as determinants of a balanced host response after the disruption of host-microbe homeostasis by pathogens. In periodontitis, Tregs play a protective role, with their natural recruitment being responsible for conversion of active into inactive lesions. With controlled-release technology, it is now possible to achieve a selective chemoattraction of Tregs to periodontal tissues, attenuating experimental periodontitis evolution due to the local control of inflammatory immune response and the generation of a pro-reparative environment.
    Journal of Dental Research 07/2014; · 4.14 Impact Factor
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    ABSTRACT: Colloidal crystals have been explored in the literature for applications in molecular electronics, photonics, sensors, and drug delivery. However, much of the research on colloidal crystals has been focused on nano-sized particles with limited attention directed towards building blocks with dimensions ranging from tens to hundreds of microns. This can be attributed, in part, to the fact that particles with greater than sub-micron dimensions do not naturally assemble in an organized fashion due to the relatively miniscule influence of thermalizing forces. Nevertheless, ordered arrays of large, micron-scale particles are of interest as a basis for the production of hierarchically structured materials with customizable pore sizes. In this work, ultrasonic agitation is being explored as a means of allowing large, non-Brownian microparticles (18-750µm) to overcome kinetic barriers to packing in the creation of close packed, highly ordered, crystalline structures. In addition we study how the energy input affects bulk particle behavior and describe several new ways to characterize colloidal crystals made from microparticles.
    Langmuir 07/2014; · 4.38 Impact Factor
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    ABSTRACT: Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiences in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 hours, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1±0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clincial standard of 56-84 topical doses over 28 days.
    Experimental Eye Research 06/2014; · 3.02 Impact Factor
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    ABSTRACT: Although approved by the United States Food and Drug Administration, enfuvirtide is rarely used in combination antiretroviral therapies (cART) to treat HIV-1 infection, primarily because of its intense dosing schedule that requires twice daily subcutaneous injection. Here, we describe the development of enfuvirtide-loaded, degradable poly(lactic-co-glycolic) acid microparticles that provide linear in vitro release of the drug over an 18 day period. This sustained release formulation could make enfuvirtide more attractive for use in cART.
    Antimicrobial Agents and Chemotherapy 12/2013; · 4.57 Impact Factor
  • Melissa H. Lash, Steven R. Little
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    ABSTRACT: Colloidal crystals have been explored in the literature for applications in molecular electronics, photonics, sensors, and drug delivery. However, much of the research on colloidal crystals has been focused on nano-sized particles with limited attention directed towards building blocks with dimensions ranging from tens to hundreds of microns. This can be attributed, in part, to the fact that large-scale particles are less prone to assemble in an organized fashion due to the relative absence of thermalizing forces. Nevertheless, ordered arrays of large particles are of interest both as a basis for the production of hierarchically structured materials as well as for tissue engineering scaffolds due to large pore sizes. In this work, ultrasonic agitation is being explored as a means of artificially “thermalizing” these particles in order to overcome kinetic barriers to packing in the creation of close packed, highly ordered, crystalline structures from large microparticles (18-750um). Using this process, we have been able to create and characterize both two- and three-dimensional structures by adjusting properties of the system and observing the changes using a variety of microscopy techniques. We are currently investigating the significance of various substrate and solution properties such as surface tension, viscosity, particle concentration and particle composition both experimentally and computationally. The interactions between the constituent particles within these colloidal formations can be estimated and analyzed, ideally providing insight into, and control over the formation of desired crystal structures.
    13 AIChE Annual Meeting; 11/2013
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    ABSTRACT: The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.
    Proceedings of the National Academy of Sciences 10/2013; · 9.81 Impact Factor
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    ABSTRACT: Glaucoma is the second leading cause of blindness in the United States. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proven effective to address non-adherence is the formation of ocular inserts, such as the Ocusert ®, whose diffusion based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug release technology provides an avenue for extending the release of practically any drug (including new drugs like BT) for as long as one month from a singular insert. Currently, no controlled release formulations for BT exist. This work outlines the development and characterization of a BT releasing ocular insert designed from poly (lactic co-glycolic) acid (PLGA)/poly ethylene glycol (PEG). We found that a formulation containing 15% PEG can be created that produces a linear BT release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use.
    Acta biomaterialia 09/2013; · 5.68 Impact Factor
  • Angewandte Chemie International Edition 09/2013; · 11.34 Impact Factor
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    ABSTRACT: The shorter, the more dispersible: An iterative, emulsion-based shortening technique has been used to reduce the length of single-walled carbon nanotubes (SWNTs) to the same order of magnitude as their diameter (ca. 1 nm), thus achieving an effectively "zero-dimensional" structure with improved dispersibility and, after hydroxylation, long-term water solubility. Finally, zero-dimensional SWNTs were positively identified using mass spectrometry for the first time.
    Angewandte Chemie International Edition 09/2013; · 11.34 Impact Factor
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    ABSTRACT: Tregs play important roles in maintaining immune homeostasis, and thus, therapies based on Treg are promising candidates for the treatment for a variety of immune-mediated disorders. These therapies, however, face the significant challenge of obtaining adequate numbers of Tregs from peripheral blood that maintains suppressive function following extensive expansion. Inducing Tregs from non-Tregs offers a viable alternative. Different methods to induce Tregs have been proposed and involve mainly treating cells with TGF-β-iTreg. However, use of TGF-β alone is not sufficient to induce stable Tregs. ATRA or rapa has been shown to synergize with TGF-β to induce stable Tregs. Whereas TGF-β plus RA-iTregs have been well-described in the literature, the phenotype, function, and migratory characteristics of TGF-β plus rapa-iTreg have yet to be elucidated. Herein, we describe the phenotype and function of mouse rapa-iTreg and reveal that these cells differ in their in vivo homing capacity when compared with mouse RA-iTreg and mouse TGF-β-iTreg. This difference in migratory activity significantly affects the therapeutic capacity of each subset in a mouse model of colitis. We also describe the characteristics of iTreg generated in the presence of TGF-β, RA, and rapa.
    Journal of leukocyte biology 07/2013; · 4.99 Impact Factor
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    ABSTRACT: Je kürzer, desto dispergierbarer: Mit einer iterativen Emulsionsmethode wurde die Länge von einwandigen Kohlenstoffnanoröhren (SWNTs) auf die Größenordnung ihres Durchmessers (ca. 1 nm) reduziert, um ,,nulldimensionale“ Strukturen mit verbesserter Dispergierbarkeit und, nach einer zusätzlichen Hydroxylierung, mit langfristiger Löslichkeit in Wasser zu erhalten. Zudem konnten nulldimensionale SWNTs erstmalig massenspektrometrisch nachgewiesen werden.
    Angewandte Chemie 01/2013; 125(43).
  • es D. Fisher, Steven R. Little, Angus W Thomson
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    ABSTRACT: Millions of Americans sustain debilitating or devastating tissue injury or loss secondary to trauma, sepsis, cancer, or congenital defects. In most cases, current prosthetics and reconstructive surgeries fail to provide optimal results in terms of aesthetic or functional outcomes. For those patients, composite tissue allotransplation (CTA)—encompassing transplantation of hands/limbs, face, abdominal wall, tongue, and larynx—may have the unique potential to restore the appearance, anatomy, and function of the damaged tissue. Although the problem of rejection in CTA is similar to that encountered in solid organ transplantation, CTA involves one of the most immunogenic organs in the body (the skin). For this reason, immunological complications following CTA will be exacerbated. In clinical CTA, the process of rejection is suppressed by systemic delivery of potent immunosuppressants. These drugs are associated with a host of deleterious side effects and, unfortunately, do little to delay the process of chronic rejection. An altertnaive approach to achieve this goal is to harness the innate homeostatic mechanisms intrinsic to the immune system. Physiologically, such a steady state is maintained by suppressive lymphocytes called regulatory T cells (Tregs). In nature, some cell types utilize a strategy such as this by releasing a chemokine that recruits Tregs. We sought to mimic this strategy synthetically to promote immune hypo-responsiveness at the site of CTA. Accordingly, our group has recently developed rationally designed controlled release microparticle (MP) systems (referred to as ChemokineMP) capable of reproducing such a Treg-recruiting chemokine gradient in vivo, leading to localization of native Tregs at the site of implantation. Furthermore, we have developed other formulations (referred to as FactorMP) capable of inducing the differentiation and expansion of Tregs from a patient's own nave CD4+ T cells, which are present in considerably greater numbers than peripheral Tregs. Recruited Tregs appear to be capable of inducing local (not systemic) immune hyporesponsiveness and resolution of destructive inflammation. Our data suggests that local recruitment of Tregs (using our mimetic controlled release chemokine formulations) may even be capable of prolonging rat hind limb CTA in the absence of long term systemic immunosuppression. Thus, we hypothesize that biomimetic, controlled release systems that release key cytokines, immunosuppressive agents, and chemokines can promote long term graft survival in a preclinical CTA model. ChemokineMP release systems were engineered using a double emulsion-evaporation method as previously described. A mathematical model of release was used to design the system such that linear release of the protein would mimic the gradient produced by tumors. Following fabrication and screening, particles were tested in an allogeneic rat hind limb transplant model. Microparticles were injected subcutaneously at the time of transplantation of hind limbs from Brown-Norway to Lewis rats and again on postoperative day 18. Treatment with ChemokineMP (one dose postoperatively and another on day 18) show enhanced survival rates when compared with blank microparticles (BlankMP) (Figures 1 and 2). Further, it was observed that ChemokineMP treated transplants maintained an intact epidermal layer with low infiltration of inflammatory cells, whereas treatment with BlankMP show a loss of the epidermal layer by postoperative day 25 with significant infiltration of inflammatory mono-nuclear cells. The outcomes of this research have the potential to dramatically impact the field of CTA and reconstructive transplantation by minimizing the need for the number, dosing and duration of systemic immunosuppression with associated long-term toxicity. Finally, these biomimetic therapies will also have broader applications unrelated to CTA such as autoimmune disorders and solid organ transplantation. Figure 1: Kaplan-Meier survival curves using control (Blank-MP) and experimental (CCL22-MP) therapies in an allogeneic rat hind limb transplant model, based on n=5 animals for each group. Figure 2: Long term surviving (>100 days) Lewis Rat with transplanted Brown- Norway Limb.
    12 AIChE Annual Meeting; 11/2012
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    ABSTRACT: System Identification and Frequency Response Techniques for the Design of Controlled Release Drug Delivery Systems Timothy Knab, Sam Rothstein, Steven R. Little, and Robert S. Parker Department of Chemical and Petroleum Engineering University of Pittsburgh, Pittsburgh, PA 15237 There is great interest in developing truly programmable controlled release systems and, to that end, numerous models have been developed. However most models are not broadly predictive and fewer still allow for direct correlation of release behavior to the controllable physical properties of the device. To address this issue, our group has recently produced a model for well-defined, programmable controlled release in vitro[1], which to our knowledge, can be applied to more drugs and polymers than systems described to date. However, the current model is limited to an idealized in vitro environment and further work is required to account for the non-ideal in vivo processes that may impact release behavior. Our goal is, for the first time, to extend the current release model to have predictive capabilities in an in vivo environment and systematically determine the most important parameters governing release in vivo. We hypothesize that tissue environment-specific effects, affecting release and transport rates, can be detected in systemic circulation and characterized using system identification techniques, namely frequency response analysis. Using the predictive power of the aforementioned model, we can synthesize particles that yield specific release profiles designed to inform the data-driven analysis. As a basis for this study, a proof of concept diffusion experiment has been developed. Changes in membrane diffusivities in a simulation of this experiment lead to changes in reservoir concentrations over time, and these differences produce identifiable changes in the frequency response characteristics as evidenced from Bode plots. This type of analysis requires a well-controlled input function -- taken from the mathematical model of controlled release - and an output signals that is easily measurable. For this we use flux, which is easily attainable from an actual experimental measurement of concentration via a derivative relationship. Over a two order of magnitude span in diffusivities these simulations show these plots changing from flat, indicating no lag, (rapid diffusion) to a rapid drop off in the magnitude and phase indicating slow diffusion and equilibration of the second tank. Experimental studies on the physical realization of the simulated diffusion cell are being compared against the simulated data as a test/validation of the experimental system and the numerical tools. Although the dynamics of diffusion cells are well studied, this system can be extended to be more analogous to in vivo physiology through experimental modifications, such as using an ECM seeded with cells as a barrier to transport or the introduction of a diffusive barrier mimicking the effects of fibroblast encapsulation of foreign microparticles. If successful, this system would provide a design framework for controlled release where exquisite control of the release system can be used to characterize -- and overcome -- potential barriers to drug release. The result is the ability to "pre-program" a microparticle for a desired release profile that results in a specified concentration profile at a location remote to the particle. The system identification techniques we propose to use require reliable, high resolution tracking of spatially disparate drug or tracker molecule concentrations. To that end, Gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) is being investigated as a potential tracking agent. Gd-DOTA concentrations at various locations within a system can be directly related to magnetic resonance imaging (MRI) T1 relaxation times. The availability of a non-invasive non-destructive imaging platform facilitates the translation of our tools to spatio-temporal analysis of experimental and in vivo systems. Initial work has focused on the design and release of Gd-DOTA from microparticles and the characterization of the diffusion profile in a polymer gel matrix. Gd-DOTA seems to be capable of coordinating with the microparticle polymer matrix, which, in effect, acts as a ligand and results in extremely delayed release compared to the model-simulated release that neglects this drug-polymer coordination. This is thought to be due to the interplay between intra-microparticle pH and Gd-DOTA charge -- an observation consistent with protein release studies also taking place in our lab. For our techniques to be successful, the effects of pH and charge needed to be included in the current model. We are currently working on a mechanistic description of these effects that will ultimately lead to an even more broadly predictive model for controlled release that can also be used in the development of a model of pre-programmable, controlled release, in vivo. [1] Rothstein, S. N., Federspiel, W. J., & Little, S. R. (2008). A simple model framework for the prediction of controlled release from bulk eroding polymer matrices. Journal of Materials Chemistry, 18(16), 1873. doi:10.1039/b718277e
    12 AIChE Annual Meeting; 10/2012
  • Shu Li, Melissa H. Lash, Steven R. Little, Joseph McCarthy
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    ABSTRACT: Sonication is a powerful dispersion technique that has been used successfully to disperse agglomerates and break partially formed bridges of nano-scaled particles. For micro-scaled particles, recent work in our lab suggests that it may also serve as a viable thermalization technique in order to promote close-packed, highly ordered colloidal crystal formation of large (non-Brownian) particles on a surface. In this study, we computationally explore the impact of sonication on particle cluster formation using the Dissipative Particle Dynamics (DPD) technique. DPD is a particle-based (i.e. Lagrangian) simulation technique that captures meso-scopic dynamics of multiphase flows by coarse-graining intermolecular forces. At its most basic, this coarse-graining results in a conservative, dissipative, and random force. Here, the effect of sonication is incorporated into the DPD method as an oscillatory external force with high frequency and low amplitude. By adding the external force from the sonication, we can inspect the microscopic details of the relative importance of the particle interactions as a function of driving parameters (frequency and amplitude) and compare our results to experimental measurements.
    12 AIChE Annual Meeting; 10/2012
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    ABSTRACT: Colloidal crystals have been explored in the literature for applications in molecular electronics, photonics, sensors, and drug delivery. However, much of the research on colloidal crystals has been focused on nano-sized particles with limited attention directed towards building blocks with dimensions ranging from tens to hundreds of microns. This can be attributed, in part, to the fact that large-scale particles are less prone to assemble in an organized fashion due to the relative absence of thermalizing forces. Nevertheless, ordered arrays of large particles are of interest both as a basis for tissue engineering scaffolds as well as a first step toward large-volume production of micron-scale “patchy particles” (anisotropically-labeled particles). In this work, ultrasonic agitation is being explored as a means of artificially “thermalizing” these particles in order to overcome kinetic barriers to packing in the creation of close packed, highly ordered, crystalline structures from large microparticles (18-100um). The film thickness is adjustable from a monolayler to a multilayer structure by changing the concentration of the solution and through a layer-by layer addition of particles. For this process, we are investigating the significance of substrate and solution properties like surface tension, viscosity, and particle concentration both experimentally and computationally. The interactions between the constituent particles within these colloidal formations can be estimated and analyzed using simulation-techniques. Simulations will not only inform as to what is occurring and ultimately achievable, but may also be used to direct the size, thickness, and quality of the overall crystal. This analysis and control over processing will ideally provide insight into, and control over the formation of a desired crystal structure.
    12 AIChE Annual Meeting; 10/2012

Publication Stats

1k Citations
335.85 Total Impact Points

Institutions

  • 2006–2014
    • University of Pittsburgh
      • • Chemical and Petroleum Engineering
      • • Bioengineering
      Pittsburgh, Pennsylvania, United States
  • 2005–2010
    • Northeastern University
      • Department of Pharmaceutical Sciences
      Boston, MA, United States
  • 2004–2010
    • Massachusetts Institute of Technology
      • Department of Chemical Engineering
      Cambridge, Massachusetts, United States
  • 2008
    • Massachusetts General Hospital
      • Department of Orthopaedic Surgery
      Boston, MA, United States