Showing papers by "Nicholas A. Peppas published in 2012"

Building Vascular Networks

Abstract: Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology.

Designing Biomaterials To Direct Stem Cell Fate

Abstract: As stem cells are a cornerstone of regenerative medicine, research efforts have been extensively focused on controlling their self-renewal and differentiation. It is well-known that stem cells are tightly regulated by a combination of physical and chemical factors from their complex extracellular surroundings; thus, conventional cell culture approaches based purely on using soluble factors to direct stem cell fate have resulted in limited success. To account for the complexities of native stem-cell niches, biomaterials are actively investigated as artificial extracellular matrices in order to mimic the natural microenvironment. This Perspective highlights important areas related to the design of biomaterials to control stem cell behavior, such as cell-responsive ligands, mechanical signals, and delivery of soluble factors.

pH‐responsive hydrogels with dispersed hydrophobic nanoparticles for the delivery of hydrophobic therapeutic agents

Abstract: To investigate the delivery of hydrophobic therapeutic agents, a new class of polymer carriers was synthesized. These carriers are composed of two components: (i) a pH-responsive hydrogel composed of methacrylic acid grafted with poly(ethylene glycol) tethers, P(MAA-g-EG), and (ii) hydrophobic poly(methyl methacrylate) (PMMA) nanoparticles. Before the P(MAA-g-EG) hydrogel was crosslinked, PMMA nanoparticles were added to the solution and upon exposure to UV light they were photoencapsulated throughout the P(MAA-g-EG) hydrogel structure. The pH-responsive behavior of P(MAA-g-EG) is capable of triggered release of a loaded therapeutic agent, such as a low molecular weight drug or protein, when it passes from the stomach (low pH) to upper small intestine (neutral pH). The introduction of PMMA nanoparticles into the hydrogel structure affected the swelling behavior, therapeutic agent loading efficiency, and solute release profiles. In equilibrium swelling conditions the swelling ratio of nanoparticle-containing hydrogels decreased with increasing nanoparticle content. Loading efficiencies of the model therapeutic agent fluorescein ranged from 38 – 51 % and increased with increasing hydrophobic content. Release studies from neat P(MAA-g-EG) and the ensuing P(MAA-g-EG) hydrogels containing nanoparticles indicated that the transition from low pH (2.0) to neutral pH (7.0) triggered fluorescein release. Maximum fluorescein release depended on the structure and hydrophobicity of the carriers used in these studies.

Protein conformational studies for macromolecularly imprinted polymers.

Abstract: CD is used to clearly show the negative impact of common ligands on the overall conformation of BSA, a typical protein template in macromolecularly imprinted polymers. This change occurs at concentrations far lower than those generally used in the literature. These findings are important as they offer insight into a potential fundamental reason for the lack of success in protein imprinting to date despite significant interest from the scientific community.

Novel strategy for the determination of UCST-like microgels network structure: effect on swelling behavior and rheology

Abstract: UCST-type interpenetrated and random copolymer microgels of polyacrylamide and poly(acrylic acid) were obtained via inverse emulsion polymerization method. The morphology of the microgels was determined by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Dynamic light scattering was used to study both the swelling behavior as a function of temperature and pH and the particle size distribution of the system. Concerning the structural characterization, a combination of the equilibrium swelling theory (Peppas–Merrill equation) and AFM technique was used to determine the mesh size of microgels. An oscillatory rheometer was used to study the viscoelastic properties. The moduli, G′ and G′′, of the microgel dispersions suggested a solid-like behaviour and structure formation. Scaling theory was applied to describe the structure formation (clustering) and the fractal dimension. The influence of composition and type of microgel, random or interpenetrated, was discussed in the above mentioned properties and behaviors.

9.20 – Hydrogels

Abstract: Hydrogels are three-dimensional network structures able to imbibe large amounts of water. Hydrogels do not typically dissolve due to chemical or physical cross-links and/or chain entanglements. They exist naturally in the form of polymer networks such as collagen or gelatin, or can be made synthetically. Environmentally sensitive hydrogels can serve a wide variety of applications because of their ability to respond to environmental changes, typically by exhibiting changes in volume. Traditional stimuli that elicit hydrogel response are pH, temperature, and ionic strength. Analytes and biomarkers including glucose, proteins, and DNA also elicit hydrogel responses. Because of such a wide variety of response triggers, hydrogels can be incorporated into sensors or actuators, or can be utilized in controlled drug delivery systems, biosensors, tissue engineering scaffolds, artificial organs, wound healing bandages, physiological membranes, contact lenses, and microfluidic valves.

Conformational studies of common protein templates in macromolecularly imprinted polymers

Abstract: Unlike the molecular imprinting of small molecule templates, molecularly imprinted polymers specific to large templates (>1,500 Da), have achieved limited success to date. Conformational stability of these labile macromolecules is one of the main factors that prevent the direct extension of successful procedures from the small molecule regime. We continue our systematic investigation of the effect of common components in macromolecular MIPs on the conformation of protein templates. Circular dichroism was used to show that frequently employed monomers and crosslinkers induce significant changes in the secondary structures of lysozyme and bovine hemoglobin. The extent to which this change occurs, at ligand concentrations far below what are typically used reported work, is cause for concern and provides as rational explanation for the lack of success in this arena. This is because a change in the template structure prior to polymerization would lead to the binding sites formed during polymerization to be specific to this alternate conformation. Subsequent studies with the macromolecule in its native state and the crosslinked network would not be successful. Using this information as a guide, we offer suggestions as to where work in macromolecular imprinted polymers should focus going forward in order for these antibody mimics to reach their vast potential as a new class of biomedical diagnostic devices.

Network structure and methanol transport dynamics in poly(methyl methacrylate)

Abstract: The effect of the polymer network structure on methanol transport dynamics in glassy polymers was investigated in both dry and plasticized disks of poly(methyl methacrylate) (PMMA) through gravimetric integral sorption studies. PMMA was synthesized by a controlled free radical polymerization mechanism, crosslinked in bulk with ethylene glycol dimethacrylate, and swollen in methanol under a variety of conditions. In the Case II transport regime, control over the transport rate was shown to depend on the glassy-state properties of the polymer, and the Case II front velocity was found to be proportional to the square root of the crosslinking density. Similarities were observed in the penetrant transport behavior of both dry and plasticized samples at high degrees of crosslinking, and the activation energy of methanol transport at low degrees of crosslinking was found to be similar for both Fickian and Case II mechanisms. © 2011 American Institute of Chemical Engineers AIChE J, 2012