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1.
Mol Pharm ; 12(10): 3776-81, 2015 Oct 05.
Article in English | MEDLINE | ID: mdl-26355438

ABSTRACT

Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity.


Subject(s)
Acrolein/metabolism , Protective Agents/chemical synthesis , Acrolein/antagonists & inhibitors , Cyclophosphamide/metabolism , HEK293 Cells/drug effects , HEK293 Cells/metabolism , Humans , Mesna/pharmacology , Polymerization , Sulfhydryl Compounds/chemical synthesis
2.
J Biomed Mater Res A ; 103(10): 3201-11, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25771925

ABSTRACT

Biopolymer-ceramic composites are thought to be particularly promising materials for bone tissue engineering as they more closely mimic natural bone. Here, we demonstrate the fabrication by electrospinning of fibrous chitosan-hydroxyapatite composite scaffolds with low (1 wt %) and high (10 wt %) mineral contents. Scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS) and unidirectional tensile testing were performed to determine fiber surface morphology, elemental composition, and tensile Young's modulus (E) and ultimate tensile strength (σUTS ), respectively. EDS scans of the scaffolds indicated that the fibers, crosslinked with either hexamethylene-1,6-diaminocarboxysulfonate (HDACS) or genipin, have a crystalline hydroxyapatite mineral content at 10 wt % additive. Moreover, FESEM micrographs showed that all electrospun fibers have diameters (122-249 nm), which fall within the range of those of fibrous collagen found in the extracellular matrix of bone. Young's modulus and ultimate tensile strength of the various crosslinked composite compositions were in the range of 116-329 MPa and 2-15 MPa, respectively. Osteocytes seeded onto the mineralized fibers were able to demonstrate good biocompatibility enhancing the potential use for this material in future bone tissue engineering applications.


Subject(s)
Chitosan/chemistry , Cross-Linking Reagents/chemistry , Materials Testing , Osteocytes/metabolism , Animals , Cell Line , Elastic Modulus , Mice , Osteocytes/cytology
3.
J Biomed Mater Res A ; 103(9): 3026-33, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25689675

ABSTRACT

Chitosan is a naturally occurring polysaccharide, which has proven to be an attractive candidate for bone tissue engineering, due to its ability to promote osteoblast mineralization. Electrospinning has become a well-established cell scaffold processing technique, as it produces a high surface area to volume fibrous material that can mimic the three dimensionality of the extracellular matrix of a cell. In this study, we have investigated the osteoblast response to two different chemically crosslinked (hexamethylene-1,6-diaminocarboxysulfonate (HDACS) and genipin) electrospun chitosan scaffolds and their film counterparts in order to determine how material chemistry influences cellular behavior in conjunction with material topology. In addition, material properties of each fiber scaffold such as porosity and tensile strength were considered. MLO-A5 osteoblast cells grown on chitosan-HDACS scaffolds were found to display a more organized cellular network, along with significantly more filopodia extensions, compared to those grown on chitosan-genipin scaffolds. After 2 days of growth on chitosan-HDACS fibers, a higher level of alkaline phosphatase expression in MLO-A5 cells was reported compared to that of either chitosan-genipin fibers or films. These results indicate that not only chemistry, but also surface topology is an important effecter of cellular behavior. Ultimately, chitosan-HDACS fiber scaffolds provided an adequate substrate for osteoblast attachment and proliferation.


Subject(s)
Biocompatible Materials/chemistry , Chitosan/chemistry , Osteoblasts/cytology , Tissue Scaffolds/chemistry , Alkaline Phosphatase/metabolism , Animals , Bone Substitutes/chemistry , Cell Adhesion , Cell Line , Cell Proliferation , Cell Survival , Cross-Linking Reagents/chemistry , Diamines/chemistry , Materials Testing , Mice , Microscopy, Electron, Scanning , Osteoblasts/metabolism , Tissue Engineering
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