Summary Deletion of the p66Shc gene results in lean and healthy mice, retards aging, and protects from aging-associated diseases, raising the question of why p66 Shc has been selected, and what is its physiological role. We have investigated survival and reproduction of p66 Shc ) ⁄ ) mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions, deletion of p66Shc was strongly counterselected. Laboratory studies revealed that p66 Shc ) ⁄ ) mice have defects in fat accumulation, thermoregulation, and reproduction, suggesting that p66Shc has been evolutionarily selected because of its role in energy metabolism. These findings imply that the health impact of targeting aging genes might depend on the specific energetic niche and caution should be exercised against premature conclusions regarding gene functions that have only been observed in protected laboratory conditions.

In tissue engineering, survival of larger constructs remains challenging due to limited supply with oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 hours. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygendepleted conditions. ABSTRACT. In tissue engineering, survival of larger constructs remains challenging due to limited supply with oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 hours. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen-depleted conditions.

The object of this study was to investigate the role of scaffold porosity on tissue ingrowth using hybrid scaffolds consisting of bladder acellular matrix and electrospun poly (lactide-co-glycolide) (PLGA) microfibers that mimic the morphological characteristics of the bladder wall in vitro and in vivo. We compared single-spun (SS) PLGA scaffolds with more porous cospun (CS) scaffolds (PLGA and polyethylene glycol). Scaffolds were characterized by scanning electron microscopy. Bladder smooth muscle cells (SMCs) were seeded, and proliferation and histological assays were performed. Sixteen rats were subjected to augmentation cystoplasty with seeded SS or CS scaffolds, morphological, and histological studies were performed 2 and 4 weeks after implantation. The porosities of SS and CS scaffolds were 73.1 ± 2.9% and 80.9 ± 1.5%, respectively. The in vitro evaluation revealed significantly deeper cell migration into CS scaffolds. The in vivo evaluation showed significant shrinkage of SS scaffolds (p = 0.019). The histological analysis revealed a bladder wall-like structure with urothelial lining and SMC infiltration in both groups. The microvessel density was significantly increased in the CS scaffolds (p < 0.001). Increasing the porosity of electrospun hybrid scaffolds is an effective strategy to enhance cell proliferation and distribution in vitro and tissue ingrowth in vivo.

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