Associations between environmental exposures and serum concentrations of Clara cell protein among elderly men in Oslo, Norway.

Cardiopulmonary morbidity and mortality is associated with several environmental exposures. Mechanistically, pathophysiological changes in the cardiopulmonary system may lead to the induction of inflammatory responses. In the present study we explored associations between environmental exposures and serum concentrations of lung Clara cell protein 16kDa, a biomarker that has recently been used to assess the integrity of the lung epithelium. Serum Clara cell protein concentrations were associated with both number of cigarettes smoked per day and number of pack-years of smoking. There was no evidence of an association between long-term exposure to ambient air pollution, as assessed at each participant's home address, and serum concentrations of CC16. However, short-term variations in both ambient air pollution and temperature were associated with increases in serum Clara cell concentrations. All findings were robust when other factors were adjusted for. These findings suggest that acute environmental exposures may compromise the integrity of the lung epithelium and lead to increased epithelial barrier permeability in the lungs of elderly men.

Manipulations in hydrogel chemistry control photoencapsulated chondrocyte behavior and their extracellular matrix production.

In engineering a cell-carrier to support cartilage growth, hydrogels provide a unique, largely aqueous environment for 3-dimensional chondrocyte culture that facilitates nutrient transport yet provides an elastic framework dictating tissue shape and supporting external loads. Although the gel environment is often >90% water, we demonstrate that slight variations in hydrogel chemistry control gel degradation, evolving macroscopic properties, and ultimately the secretion and distribution of extracellular matrix molecules. Specifically, biodegradable poly(ethylene glycol)-co-poly(lactic acid) hydrogels were fabricated via photopolymerization. When chondrocytes were photoencapsulated in these gels, changes in the poly(ethylene glycol)-co-poly(lactic acid) repeat unit ratio from 19 to 7 increased total collagen synthesis 2.5-fold after 6 weeks in vitro. Furthermore, the ratio of collagen to glycosaminoglycans varied from glycosaminoglycan-rich, 0.33 +/- 0.13, to collagen-rich, 4.58 +/- 1.21, depending on gel chemistry and in vitro versus in vivo culture environment. By tuning scaffold chemistry, and subsequently, gel structure and degradation behavior, we can better guide tissue evolution and development.

Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production.

A major challenge when designing cell scaffolds for chondrocyte delivery in vivo is creating scaffolds with sufficient mechanical properties to restore initial function while simultaneously controlling temporal changes in the gel structure to facilitate tissue formation. To address this design challenge, degradable photocrosslinked hydrogels based on poly(ethylene glycol) were investigated. To alter the gel's initial mechanical properties, hydrogels were fabricated by varying the initial macromer concentration from 10% to 15% to 20%. A twofold increase in macromer concentration resulted in an eightfold increase in the initial compressive modulus from 60 to 500 kPa. Gel degradation was tailored by incorporating fast-degrading crosslinks that enable maximal extracellular matrix (ECM) diffusion with time and a minimal number of nondegrading (or slowly degrading) crosslinks to maintain scaffold integrity and prevent complete gel erosion during tissue formation. Chondrocytes encapsulated in these gels produced cartilaginous tissue rich in glycosaminoglycans and collagen as seen biochemically and histologically. Interestingly, mass loss appeared to more closely match tissue secretion in gels fabricated from a 15% macromer concentration. However, the spatial ECM distribution was grossly similar in all three gels. By tailoring gel degradation and controlling network evolution during degradation, gels with optimal properties can be fabricated to support initially physiologic compressive loads while simultaneously supporting the formation of a neotissue.