High-throughput screening of a small molecule library for promoters and inhibitors of mesenchymal stem cell osteogenic differentiation.

The use of high-throughput screening (HTS) techniques has long been employed by the pharmaceutical industry to increase discovery rates for new drugs that could be useful for disease treatment, yet this technology has only been minimally applied in other applications such as in tissue regeneration. In this work, an assay for the osteogenic differentiation of human mesenchymal stem cells (hMSCs) was developed and used to screen a library of small molecules for their potential as either promoters or inhibitors of osteogenesis, based on levels of alkaline phosphatase activity and cellular viability. From a library of 1,040 molecules, 36 promoters, and 20 inhibitors were identified as hits based on statistical criteria.

Identification of osteoconductive and biodegradable polymers from a combinatorial polymer library.

Combinatorial polymer syntheses are now being utilized to create libraries of materials with potential utility for a wide variety of biomedical applications. We recently developed a library of photopolymerizable and biodegradable poly(beta-amino ester)s (PBAEs) that possess a range of tunable properties. In this study, the PBAE library was assessed for candidate materials that met design criteria (e.

High-throughput and combinatorial technologies for tissue engineering applications.

As the field of tissue engineering progresses, new technology is essential to accelerate the identification of potentially translatable approaches for the repair of tissues damaged due to disease or trauma. The development of high-throughput and combinatorial technologies is helping to speed up research that is applicable to all aspects of the tissue engineering paradigm. This diverse technology can be used for both the rapid synthesis of polymers and their characterization with respect to local and bulk properties in a high-throughput fashion.

Electrospinning of photocrosslinked and degradable fibrous scaffolds.

Electrospun fibrous scaffolds are being developed for the engineering of numerous tissues. Advantages of electrospun scaffolds include the similarity in fiber diameter to elements of the native extracellular matrix and the ability to align fibers within the scaffold to control and direct cellular interactions and matrix deposition. To further expand the range of properties available in fibrous scaffolds, we developed a process to electrospin photocrosslinkable macromers from a library of multifunctional poly(beta-amino ester)s.

Controlling poly(beta-amino ester) network properties through macromer branching.

Photopolymerizable and degradable biomaterials are becoming important in the development of advanced materials in the fields of tissue engineering, drug delivery, and microdevices. We have recently developed a library of poly(beta-amino ester)s (PBAEs) that form networks with a wide range of mechanical properties and degradation rates that are controlled by simple alterations in the macromer molecular weight or chemical structure. In this study, the influence of macromer branching on network properties was assessed by adding the trifunctional monomer pentaerythritol triacrylate (PETA) during synthesis.

Influence of macromer molecular weight and chemistry on poly(beta-amino ester) network properties and initial cell interactions.

A library of photocrosslinkable poly(beta-amino ester)s (PBAEs) was recently synthesized to expand the number of degradable polymers that can be screened and developed for a variety of biological applications. In this work, the influence of variations in macromer chemistry and macromer molecular weight (MMW) on network reaction behavior, overall bulk properties, and cell interactions were investigated. The MMW was controlled through alterations in the initial diacrylate to amine ratio (> or =1) during synthesis and decreased with an increase in this ratio.

Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.

Vascular endothelial cells (EC) are an important target of estrogen action through both the classical genomic (i.e. nuclear-initiated) activities of estrogen receptors alpha and beta (ERalpha and ERbeta) and the rapid "non-genomic" (i.