Microsphere-Based Osteochondral Scaffolds Carrying Opposing Gradients Of Decellularized Cartilage And Demineralized Bone Matrix

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Biomaterials Science & Engineering, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsbiomaterials.6b00071.Extracellular matrix (ECM) “raw materials” such as demineralized bone matrix (DBM) and cartilage matrix have emerged as leading scaffolding materials for osteochondral regeneration owing to their capacity to facilitate progenitor/resident cell recruitment, infiltration, and differentiation without adding growth factors. Scaffolds comprising synthetic polymers are sturdy yet generally lack cues for guiding cell differentiation. We hypothesized that opposing gradients of decellularized cartilage (DCC) and DBM in polymeric microsphere-based scaffolds would provide superior regeneration compared to polymer-only scaffolds in vivo. Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds were fabricated, either with opposing gradients of DCC and DBM encapsulated (GRADIENT) or without DCC and DBM (BLANK control), and implanted into rabbit osteochondral defects in medial femoral condyles. After 12 weeks, gross morphological evaluation showed that the repair tissue in about 30% of the implants was either slightly or significantly depressed, hinting toward rapid polymer degradation in scaffolds from both of the groups. Additionally, no differences were observed in gross morphology of the repair tissue between the BLANK and GRADIENT groups. Mechanical testing revealed no significant differences in model parameter values between the two groups. Histological observations demonstrated that the repair tissue in both of the groups was fibrous in nature with the cells demonstrating notable proliferation and matrix deposition activity. No adverse inflammatory response was observed in any of the implants from the two groups. Overall, the results emphasize the need to improve the technology in terms of altering the DBM and DCC concentrations, and tailoring the polymer degradation to these concentrations.R01 AR056347Kansas Bioscience Authority Rising Star Awar

Path learning: the role of positive or neutral landmark on environment recall

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Bidirectional electrical communication between smooth muscle and endothelial cells in the pig coronary artery

Using strips of the left descending branch of the pig coronary artery in vitro, we show that smooth muscle cells are hyperpolarized by isoproterenol, a beta-agonist, independently of the presence or absence of intact endothelium. This hyperpolarization is transmitted to the lining endothelial cells in intact coronary strips. On the contrary, the cultured endothelial cells, without contact with smooth muscles, are not hyperpolarized by the beta-agonist. This shows that, in addition to the hyperpolarizations that flow from the endothelium to the media in response to kinins, electrical signals are also transmitted in the opposite direction, from the smooth muscles to the lining endothelial cells. In an attempt to test whether electrical coupling through gap junctions is implicated in the transmission of hyperpolarizations between the endothelial and the smooth muscle cells, we used halothane, a gap junction uncoupler. We observed that halothane does not inhibit the transmission of kinin hyperpolarizations from the endothelium to the smooth muscles, whereas it inhibits the transmission of isoproterenol hyperpolarization in the reverse direction