Cell‐Friendly Inverse Opal‐Like Hydrogels for a Spatially Separated Co‐Culture System

Three‐dimensional macroporous scaffolds have extensively been studied for cell‐based tissue engineering but their use is mostly limited to mechanical support for cell adhesion and growth on the surface of macropores. Here, a templated fabrication method is described to prepare cell‐friendly inverse opal‐like hydrogels (IOHs) allowing both cell encapsulation within the hydrogel matrix and cell seeding on the surface of macropores. Ionically crosslinked alginate microbeads and photocrosslinkable biocompatible polymers are used as a sacrificial template and as a matrix, respectively. The alginate microbeads are easily removed by a chelating agent, with minimal toxicity for the encapsulated cells during template removal. The outer surface of macropores in IOHs can also provide a space for cell adherence. The cells encapsulated or attached in IOHs are able to remain viable and to proliferate over time. The elastic modulus and cell‐adhesion properties of IOHs can be easily controlled and tuned. Finally, it is demonstrated that IOH can be used to co‐culture two distinct cell populations in different spatial positions. This cell‐friendly IOH system provides a 3D scaffold for organizing different cell types in a controllable microenvironment to investigate biological processes such as stem cell niches or tumor microenvironments.

     

Generalized Irreducible Divisor Graphs

In 1988, Beck introduced the notion of a zero-divisor graph of a commutative rings with 1. There have been several generalizations in recent years. In particular, in 2007 Coykendall and Maney developed the irreducible divisor graph. Much work has been done on generalized factorization, especially τ-factorization. The goal of this paper is to synthesize the notions of τ-factorization and irreducible divisor graphs in domains. We will define a τ-irreducible divisor graph for nonzero non unit elements of a domain. We show that, by studying τ-irreducible divisor graphs, we find equivalent characterizations of several finite τ-factorization properties.     

Synthesis, structural characterization, in vitro anti-proliferative effect and cell cycle analysis of N-(ferrocenyl)benzoyl dipeptide esters

N-ortho, meta and para-(ferrocenyl)benzoyl dipeptide esters 2-10 were prepared by coupling ferrocenyl benzoic acids 1(ortho, meta and para) to the dipeptide ethyl esters GlyAbu(OEt) 2-4, GlyNva(OEt) 5-7 and GlyNle(OEt) 8-10 in the presence of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole. The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry and cyclic voltammetry. The cytotoxicity of 3, 6 and 9 versus H1299 lung cancer cells were 10.5 μM, 19.1 μM and 18.9 μM, respectively, whereas N-{meta-(ferrocenyl)-benzoyl}-glycine-l-alanine ethyl ester 11 and N-{para-(ferrocenyl)-benzoyl}-glycine-l-alanine ethyl ester 12 gave IC₅₀ values of 4.0 and 6.6 μM, respectively. Therefore, an increase in alkyl chain length of the second amino acid also increases the IC₅₀ values. Cell cycle analysis of N-{ortho-(ferrocenyl)-benzoyl}-glycine-l-alanine ethyl ester 13 suggests a block in the G2/M phase of the cell cycle.     

Three-dimensional critical behavior with 2D, 1D, and 0D dimensionality crossover: surface and edge specific heats

The critical behavior at a second order phase transition is characterized by the divergence of the correlation length xi. We have studied the superfluid transition of 4He in a series of experimental cells in which this divergence of xi is modified due to finite-size confinement. In particular, the design of these cells is such that the smallest dimension is kept the same, 1 microm, but the geometry is such that one obtains crossover to dimensionality of 2, 1, and 0. This corresponds to films, channels, and boxes filled with helium. We measure the specific heat and compare these results with theoretical expectations. We identify surface and line specific heat contributions by analyzing the deviation of the specific heat from its behavior in the thermodynamic limit. The design of these cells is made possible by a combination of silicon lithography and direct wafer bonding.     

Bioinspired growth of crystalline carbonate apatite on biodegradable polymer substrata

Mineralization in biological systems is a widespread, yet incompletely understood phenomenon involving complex interactions at the biomacromolecule-mineral nucleus interface. This study was aimed at understanding and controlling mineral formation in a poly(alpha-hydroxy ester) model system, to gain insight into biological mineralization processes and to develop biomaterials for orthopaedic tissue regeneration. We specifically hypothesized that providing a high surface density of anionic functional groups would enhance nucleation and growth of bonelike mineral following exposure to simulated body fluids (SBF). Polymer surface functionalization was achieved via hydrolysis of 85:15 poly(lactide-co-glycolide) (PLG) films. This treatment led to an increase in surface carboxylic acid and hydroxyl groups, resulting in a substantial increase in polymer surface energy from 42 to 49 dynes/cm2. Treated polymers exhibited a 3-fold increase in heterogeneous mineral grown and growth of a continuous mineral film on the polymer surface. The mineral grown on PLG surfaces is a carbonate apatite, the major mineral component of vertebrate bone tissue. Mineral crystal size and morphology were dependent on the solution characteristics but unaffected by the degree of surface prehydrolysis. The mechanism of heterogeneous carbonate apatite growth was examined via ion binding assays, which indicated that calcium binding is mediated independently by the presence of soluble phosphate counterions and surface functional groups. These findings indicate that poly(alpha-hydroxy ester) materials can be readily mineralized using a biomimetic process, and that the impetus for mineral nucleation in this system appears more complicated than the simple electrostatic interactions proposed in previous biomineralization theory.     

One‐Step Microfluidic Fabrication of Polyelectrolyte Microcapsules in Aqueous Conditions for Protein Release

We report a microfluidic approach for one‐step fabrication of polyelectrolyte microcapsules in aqueous conditions. Using two immiscible aqueous polymer solutions, we generate transient water‐in‐water‐in‐water double emulsion droplets and use them as templates to fabricate polyelectrolyte microcapsules. The capsule shell is formed by the complexation of oppositely charged polyelectrolytes at the immiscible interface. We find that attractive electrostatic interactions can significantly prolong the release of charged molecules. Moreover, we demonstrate the application of these microcapsules in encapsulation and release of proteins without impairing their biological activities. Our platform should benefit a wide range of applications that require encapsulation and sustained release of molecules in aqueous environments.