A thermo-responsive poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone}-b-poly(γ-octyloxy-ε-caprolactone) (PMEEECL-b-POCTCL) diblock copolymer was synthesized by ring-opening polymerization using tin octanoate (Sn(Oct)(2)) catalyst and a fluorescent dansyl initiator. The PMEEECL-b-POCTCL had a lower critical solution temperature (LCST) of 38 °C, and it was employed to prepare thermally responsive micelles. Nile Red and Doxorubicin (DOX) were loaded into the micelles, and the micellar stability and drug carrying ability were investigated. The size and the morphology of the cargo-loaded micelles were determined by DLS, AFM, and TEM. The Nile-Red-loaded polymeric micelles were found to be stable in the presence of both fetal bovine serum and bovine serum albumin over a 72 h period and displayed thermo-responsive in vitro drug release. The blank micelles showed a low cytotoxicity. As comparison, the micelles loaded with DOX showed a much higher in vitro cytotoxicity against MCF-7 human breast cancer cell line when the incubation temperature was elevated above the LCST. Confocal laser scanning microscopy was used to study the cellular uptake and showed that the DOX-loaded micelles were internalized into the cells via an endocytosis pathway.

The effect of the core substituent structure on the micellar behavior of thermoresponsive amphiphilic poly(εcaprolactone) diblock copolymer micelles was investigated through a combination of experimental and computational methods. The polycaprolactone (PCL) amphiphilic block copolymers used in this study consisted of a hydrophilic poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} block, which also endowed the polymer with thermoresponsiveness, and various hydrophobic poly(γ-alkoxy-ε-caprolactone) blocks. Five different substituents have been attached to the γ-position of the ε-caprolactone of the hydrophobic block, namely octyloxy, ethylhexyloxy, ethoxy, benzyloxy, and cyclohexylmethoxy, which self-assembled in aqueous media to generate the core of the micelles. All five synthesized diblock copolymers formed micelles in water and displayed thermoresponsive behavior with lower critical solution temperature (LCST) in the range of 36−39 °C. The impact of different substituents on the micelle properties such as size, stability, and phase transition behavior was investigated. Drug loading and release properties were also studied by employing doxorubicin (DOX) as payload. Molecular dynamics modeling was used to predict the variation of particle size, free volume, and drug loading capacity. The drug loading capacity predicted from molecular dynamics simulation was found to be comparable with the experimental data, which suggests that molecular dynamic simulations may be a useful tool to provide valuable selection criteria for the engineering of polymeric micelles with tunable size and drug loading capacity.

Scaffold architecture, surface topography, biochemical and mechanical cues have been shown to significantly improve cellular events and in vivo tissue regeneration. Specifically electrospun nanofiber matrices have gained tremendous interest due to their intrinsic structural resemblance to native tissue extracellular matrix (ECM). The present study reports on the electrospun nanofiber matrices of polycaprolactone (PCL)-chitosan (CS) blends and effect of type I collagen surface functionalization in regulating rat bone marrow derived stromal cells (rBMSCs) differentiation into osteogenic lineage. Collagen was covalently attached to blend nanofibers via carbodiimide (EDC) coupling. Bead-free smooth nanofibers (diameter-700-850 nm) obtained at the optimized conditions of polymer concentration and electrospinning parameters were used for the study. EDC collagen coupling resulted in 0.120+/-0.016 micro g of collagen immobilization onto a 1 cm2 area of the PCL/CS nanofibers, which was 2.6-folds higher than the amount of collagen that can be retained by physical adsorption. Significantly improved rBMSCs adhesion, spreading, proliferation and osteogenic differentiation was observed on the collagen functionalized COL-PCULCS nanofiber matrices as compared to control groups. Osteogenic phenotypic markers such as alkaline phosphatase (ALP) activity and mineralization were found to be significantly higher on COL-PCL/CS nanofiber matrices as compared to controls. Elevated gene expression profiles of osteogenic markers such as osteocalcin (0CN), osteopontin (OPN) and ALP further corroborate the osteoinductive nature of the collagen functionalized PCL/CS nanofiber matrices. These fiber matrices and modification techniques could be extended to other scaffold systems for tissue engineering applications.

Injectable hydrogels have attracted a great deal of attention as cell carriers and bioactive agents in regenerative medicine due to their ability to fill complex three-dimensional (3D) tissue gaps and relative ease of in vivo administration. Polysaccharidebased hydrogels can provide microenvironments that favor tissue regeneration and biocompatibility due to their chemical similarities with native extracellular matrix components. This manuscript reports the in vitro application of an injectable chitosan-based polysaccharide hydrogel for cell and protein delivery. Crosslinked hydrogels were produced by the reaction between the amino functionality of chitosan and the aldehyde of dextran aldehyde resulting in an imine bond (Schiff 's base) formation in aqueous solutions. This approach eliminated the use of additional crosslinking agents which may pose undesired side effects regarding cytotoxicity and biocompatibility. Additionally, we demonstrate versatility of the gel in terms of its fabrication, and ability to alter mechanical properties by changing the crosslinking extent due to aldehyde content. Bovine serum albumin (BSA), used as a model protein, followed a steady release pattern from the gel. BSA release was dependent on the extent of hydrogel crosslinking. Increase in crosslinking extent resulted in improved mechanical properties and sustained release of BSA. Human fetal osteoblasts encapsulated into the hydrogel showed at least 70% viability and continued to proliferate under in vitro culture. V C 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39934.

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