Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair

OBJECTIVE: As our population ages, treatment for joint pain associated with articular cartilage damage is becoming a prevalent challenge. Accordingly, this work investigates local delivery of two regulatory proteins - transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) - to cartilage defects from degradable scaffolds as a potential strategy for improving cartilage repair. METHOD: The effects of TGF-beta1 and/or IGF-1 delivery on osteochondral repair in adult rabbits were examined through histomorphometric analysis of 11 markers of osteochondral repair. RESULTS: Complete scaffold degradation occurred allowing for assessment of the healing response at 12 weeks post-surgery. When compared to untreated defects, higher scores were observed with IGF-1-treated defects for the six markers of neo-surface repair: neo-surface morphology, cartilage thickness, surface regularity, chondrocyte clustering, and the chondrocyte/glycosaminoglycan content of the neo-surface and the cartilage surrounding the defect. Surprisingly, the benefits of IGF-1 delivery were not maintained when this growth factor (GF) was co-delivered with TGF-beta1, despite numerous in vitro reports of the combinatory actions of these GFs. CONCLUSIONS: While localized delivery of IGF-1 may be a promising repair strategy, further in vivo assessment is necessary, since fibrous tissue was commonly observed in the neo-surface of all treatment groups. More importantly, this study highlights the need to rigorously examine GF interactions in the wound healing environment and demonstrates that in vitro observations do not directly translate to the in vivo setting

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Visualization of the lipid barrier and measurement of lipid pathlength in human stratum corneum

Detailed models of solute transport through the stratum corneum (SC) require an interpretation of apparent bulk diffusion coefficients in terms of microscopic transport properties. Modern microscopy techniques provide a tool for evaluating one key property—lipid pathway tortuosity—in more detail than previously possible. Microscopic lipid pathway measurements on alkali expanded human SC stained with the lipid-soluble dyes methylene blue, Nile red, and oil red O are described. Brightfield, differential interference contrast, fluorescence, and laser scanning confocal optics were employed to obtain 2-dimensional (2-D) and 3-dimensional (3-D) images. The 2-D techniques clearly outlined the corneocytes. Confocal microscopy using Nile red yielded a well-delineated 3-D structure of expanded SC. Quantitative assessment of the 2-D images from a small number of expanded SC samples led to an average value of 3.7 for the ratio of the shortest lipid-continuous pathway to the width of the membrane. This was corrected for the effect of alkaline expansion to arrive at an average value of 12.7 for the same ratio prior to swelling