In the U.S., 30% of adults suffer joint pain, most commonly in the knee, which severely limits mobility and is often attributed to injury of cartilage and underlying bone in the joint. Current treatment methods such as microfracture result in less resilient fibrocartilage with eventual failure; autografting can cause donor site morbidity and poor integration. To overcome drawbacks in treatment, tissue engineers can design cell-instructive biomimetic scaffolds using biocompatible materials as alternate therapies for osteochondral defects. Nanofibrous poly (L-lactic acid) (PLLA) scaffolds of uniform, spherical, interconnected and well-defined pore sizes that are fabricated using a thermally-induced phase separation and sugar porogen template method create an extracellular matrix-like environment which facilitates cell adhesion and proliferation. Herein we report that chondrogenesis and endochondral ossification of rabbit and human bone marrow stromal cells (BMSCs) can be controlled by scaffold pore architecture, particularly pore size. Small-pore scaffolds support enhanced chondrogenic differentiation in vitro and cartilage formation in vivo compared to large-pore scaffolds. Endochondral ossification is prevented in scaffolds with very small pore sizes; pore interconnectivity is critical to promote capillary ingrowth for mature bone formation. These results provide a novel strategy to control tissue regenerative processes by tunable architecture of macroporous nanofibrous scaffolds.

To examine how readers of Chinese and English take advantage of orthographic and phonological features in reading, the authors investigated the effects of spelling errors on reading text in Chinese and English using the error disruption paradigm of M. Daneman and E. Reingold (1993). Skilled readers in China and the United States read passages in their native language that contained occasional spelling errors. Results showed that under some circumstances very early phonological activation can be identified in English, but no evidence for early phonology was found in Chinese. In both languages, homophone errors showed a benefit in measures of later processing, suggesting that phonology helps readers recover from the disruptive effects of errors. These results suggest that skilled readers take advantage of the special features of particular orthographies but that these orthographic effects may be most pronounced in the early stages of lexical access.

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Nucleus pulposus grafts are needed for patients requiring replacement of their degenerated intervertebral discs. Bone marrow-derived mesenchymal stem cells (MSCs) are potential autologous stem cell source for the nucleus pulposus regeneration. One of the key issues of constructing functional nucleus pulposus using MSCs, however, is to differentiate MSCs into nucleus pulposus phenotype in vitro and to maintain their phenotypic stability in vivo. In this study, three-dimensional (3D) nanofibrous poly(L-lactide) (PLLA) scaffolds were seeded with multi-potent rabbit MSCs and the constructs were induced along nucleus pulposus development routes in a hypoxia chamber (2% O2) in the presence of TGF-β1. It was found that nanofibrous scaffold could support the differentiation of rabbit MSCs towards a nucleus pulposus-like phenotype in vitro, as evidenced by upregulated expression of a few important nucleus pulposus-associated genes (aggrecan, type II collagen and Sox-9), abundant deposition of extracellular matrix (glycosaminoglycan (GAG) and type II collagen), and the continuous expression of the nucleus pulposus-specific marker, hypoxia-inducible factor (HIF)-1α. The subcutaneous implantation results confirmed that hypoxic induction before implantation could help the constructs to retain their phenotype and resist calcification in vivo. Therefore, the above data showed the promise of using 3D nanofibrous scaffolds in combination with TGF-β1 and hypoxic induction to regenerate functional nucleus pulposus grafts for intervertebral disc replacement.