Surface hydroxylation of styrene-butadiene-styrene block copolymers for biomaterials.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1974.Vita.Bibliography: leaves 262-270.Sc.D

The blood compatibility challenge. Part 3: Material associated activation of blood cascades and cells

The final publication is available at Elsevier via https://doi.org/10.1016/j.actbio.2019.06.020. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Following protein adsorption/activation which is the first step after the contact of material surfaces and whole blood (part 2), fibrinogen is converted to fibrin and platelets become activated and assembled in the form of a thrombus. This thrombus formation is the key feature that needs to be minimized in the creation of materials with low thrombogenicity. Further aspects of blood compatibility that are important on their own are complement and leukocyte activation which are also important drivers of thrombus formation. Hence this review summarizes the state of knowledge on all of these cascades and cells and their interactions. For each cascade or cell type, the chapter distinguishes statements which are in widespread agreement from statements where there is less of a consensus

An NF-κB and Slug Regulatory Loop Active in Early Vertebrate Mesoderm

BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IκB kinase-mediated activation of the bipartite transcription factor NF-κB. NF-κB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-κB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail–NF-κB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease

A Modular Approach to Cardiac Tissue Engineering

Functional cardiac tissue was prepared using a modular tissue engineering approach with the goal of creating vascularized tissue. Rat aortic endothelial cells (RAEC) were seeded onto submillimeter-sized modules made of type I bovine collagen supplemented with Matrigel™ (25% v/v) embedded with cardiomyocyte (CM)-enriched neonatal rat heart cells and assembled into a contractile, macroporous, sheet-like construct. Modules (without RAEC) cultured in 10% bovine serum (BS) were more contractile and responsive to external stimulus (lower excitation threshold, higher maximum capture rate, and greater en face fractional area changes) than modules cultured in 10% fetal BS. Incorporating 25% Matrigel in the matrix reduced the excitation threshold and increased the fractional area change relative to collagen only modules (without RAEC). A coculture medium, containing 10% BS, low Mg2+ (0.814 mM), and normal glucose (5.5 mM), was used to maintain RAEC junction morphology (VE-cadherin) and CM contractility, although the responsiveness of CM was attenuated with RAEC on the modules. Macroporous, sheet-like module constructs were assembled by partially immobilizing a layer of modules in alginate gel until day 8, with or without RAEC. RAEC/CM module sheets were electrically responsive; however, like modules with RAEC this responsiveness was attenuated relative to CM-only sheets. Muscle bundles coexpressing cardiac troponin I and connexin-43 were evident near the perimeter of modules and at intermodule junctions. These results suggest the potential of the modular approach as a platform for building vascularized cardiac tissue

Chimeric Vessel Tissue Engineering Driven by Endothelialized Modules in Immunosuppressed Sprague-Dawley Rats

Modular tissue engineering is a means of building functional, vascularized tissues using small (∼1 mm long × 0.5 mm diameter) components. While this approach is being explored for its utility in adipose and cardiac tissue engineering and in islet transplantation, the initial question in this study was to assess the fate of the endothelial cells (EC) after transplantation delivered on the surface of modules, without an embedded cell. Rat aortic EC-covered collagen gel modules were transplanted into the omental pouch of allogeneic (outbred) Sprague-Dawley rats with and without immunosuppressive drug treatment (atorvastatin and tacrolimus) for 3–60 days. There was a significant increase in vessel density at all time points in the drug treated rats as compared to untreated rats. Green fluorescent protein (GFP)-positive donor rat aortic EC migrated from the surface of the modules and formed primitive vessels by day 7. In the untreated rats, the GFP-positive cells were not seen after day 7. In drug-treated rats, GFP-positive vessels matured over time, accumulated erythrocytes, were supported by host smooth muscle cells, and formed chimeric vessels that survived until day 60. This resulted in the formation of a densely vascularized, perfusable network by day 60. To our knowledge, this is the first study that demonstrates that primary unmodified EC, without the addition of supporting cells, form a chimeric and stable vascular bed in allogeneic, although drug-treated, animals