A human lung alveolus-on-a-chip model of acute radiation-induced lung injury.

Acute exposure to high-dose gamma radiation due to radiological disasters or cancer radiotherapy can result in radiation-induced lung injury (RILI), characterized by acute pneumonitis and subsequent lung fibrosis. A microfluidic organ-on-a-chip lined by human lung alveolar epithelium interfaced with pulmonary endothelium (Lung Alveolus Chip) is used to model acute RILI in vitro. Both lung epithelium and endothelium exhibit DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6 h of radiation exposure, although greater damage is observed in the endothelium.

Modeling mucus physiology and pathophysiology in human organs-on-chips.

The surfaces of human internal organs are lined by a mucus layer that ensures symbiotic relationships with commensal microbiome while protecting against potentially injurious environmental chemicals, toxins, and pathogens, and disruption of this layer can contribute to disease development. Studying mucus biology has been challenging due to the lack of physiologically relevant human in vitro models. Here we review recent progress that has been made in the development of human organ-on-a-chip microfluidic culture models that reconstitute epithelial tissue barriers and physiologically relevant mucus layers with a focus on lung, colon, small intestine, cervix and vagina.

Bioengineered Tissue Model of Fibroblast Activation for Modeling Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a complex disease of unknown etiology with no current curative treatment. Modeling pulmonary fibrotic (PF) tissue has the potential to improve our understanding of IPF disease progression and treatment. Rodent animal models do not replicate human fibroblastic foci (Hum-FF) pathology, and current iterations of model systems (e.

Gradient platform for combinatorial screening of thermoset polymers for biomedical applications.

The goal of this work was to design a device for rapid screening of crosslinked thermoset polymers. This gradient curing platform is capable of yielding a library of polyesters with systematically varying mechanical and physicochemical properties and the resultant cellular response. A library of poly(xylitolsebacate) polyesters was prepared in this device by differential curing to yield a gradient polymer.

Controlled release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups.

Controlled Release of Usnic Acid from Biodegradable Polyesters to Inhibit Biofilm Formation.

Controlled and sustained release of antibacterial drugs is a promising approach to address challenges related to bacterial infections in biomedical implants. Biocompatible polyols like xylitol and mannitol are frequently used to synthesize cross-linked, biodegradable polyesters. Xylitol-based adipoyl and sebacoyl polyesters were synthesized by a catalyst free melt polyesterification technique.

Poly(ester amide)s from Soybean Oil for Modulated Release and Bone Regeneration.

Designing biomaterials for bone tissue regeneration that are also capable of eluting drugs is challenging. Poly(ester amide)s are known for their commendable mechanical properties, degradation, and cellular response. In this regard, development of new poly(ester amide)s becomes imperative to improve the quality of lives of people affected by bone disorders.

Physical insights into salicylic acid release from poly(anhydrides).

Salicylic acid (SA) based biodegradable polyanhydrides (PAHs) are of great interest for drug delivery in a variety of diseases and disorders owing to the multi-utility of SA. There is a need for the design of SA-based PAHs for tunable drug release, optimized for the treatment of different diseases. In this study, we devised a simple strategy for tuning the release properties and erosion kinetics of a family of PAHs.

Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity.

Unlabelled: Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity.

Controlled Release of Salicylic Acid from Biodegradable Cross-Linked Polyesters.

The purpose of this work was to develop a family of cross-linked poly(xylitol adipate salicylate)s with a wide range of tunable release properties for delivering pharmacologically active salicylic acid. The synthesis parameters and release conditions were varied to modulate polyester properties and to understand the mechanism of release. Varying release rates were obtained upon longer curing (35% in the noncured polymer to 10% in the cured polymer in 7 days).

Combinatorial approach to develop tailored biodegradable poly(xylitol dicarboxylate) polyesters.

The objective of this work was to develop a versatile strategy for preparing biodegradable polymers with tunable properties for biomedical applications. A family of xylitol-based cross-linked polyesters was synthesized by melt condensation. The effect of systematic variation of chain length of the diacid, stoichiometric ratio, and postpolymerization curing time on the physicochemical properties was characterized.