Carbon nanotube (CNT) and nanofibrillated cellulose (NFC) reinforcement effect on thermoplastic polyurethane (TPU) scaffolds fabricated via phase separation using dimethyl sulfoxide (DMSO) as solvent.

Although phase separation is a simple method of preparing tissue engineering scaffolds, it suffers from organic solvent residual in the scaffold. Searching for nontoxic solvents and developing effective solvent removal methods are current challenges in scaffold fabrication. In this study, thermoplastic polyurethane (TPU) scaffolds containing carbon nanotubes (CNTs) or nanofibrillated cellulose fibers (NFCs) were prepared using low toxicity dimethyl sulfoxide (DMSO) as a solvent. The effects of two solvent removal approaches on the final scaffold morphology were studied. The freeze drying method caused large pores, with small pores on the pore walls, which created connections between the pores. Meanwhile, the leaching and freeze drying method led to interconnected fine pores with smaller pore diameters. The nucleation effect of CNTs and the phase separation behavior of NFCs in the TPU solution resulted in significant differences in the microstructures of the resulting scaffolds. The mechanical performance of the nanocomposite scaffolds with different morphologies was investigated. Generally, the scaffolds with a fine pore structure showed higher compressive properties, and both the CNTs and NFCs improved the compressive properties of the scaffolds, with greater enhancement found in TPU/NFC nanocomposite scaffolds. In addition, all scaffolds showed good sustainability under cyclical load bearing, and the biocompatibility of the scaffolds was verified via 3T3 fibroblast cell culture.

Electrospinning thermoplastic polyurethane/graphene oxide scaffolds for small diameter vascular graft applications.

Fabrication of small diameter vascular grafts plays an important role in vascular tissue engineering. In this study, thermoplastic polyurethane (TPU)/graphene oxide (GO) scaffolds were fabricated via electrospinning at different GO contents as potential candidates for small diameter vascular grafts. In terms of mechanical and surface properties, the tensile strength, Young's modulus, and hydrophilicity of the scaffolds increased with an increase of GO content while plasma treatment dramatically improved the scaffold hydrophilicity. Mouse fibroblast (3T3) and human umbilical vein endothelial cells (HUVECs) were cultured on the scaffolds separately to study their biocompatibility and potential to be used as vascular grafts. It was found that cell viability for both types of cells, fibroblast proliferation, and HUVEC attachment were the highest at a 0.5wt.% GO loading whereas oxygen plasma treatment also enhanced HUVEC viability and attachment significantly. In addition, the suture retention strength and burst pressure of tubular TPU/GO scaffolds containing 0.5wt.% GO were found to meet the requirements of human blood vessels, and endothelial cells were able to attach to the inner surface of the tubular scaffolds. Platelet adhesion tests using mice blood indicated that vascular scaffolds containing 0.5% GO had low platelet adhesion and activation. Therefore, the electrospun TPU/GO tubular scaffolds have the potential to be used in vascular tissue engineering.

Incorporation of poly(ethylene glycol) grafted cellulose nanocrystals in poly(lactic acid) electrospun nanocomposite fibers as potential scaffolds for bone tissue engineering.

Poly(ethylene glycol) (PEG)-grafted cellulose nanocrystals (CNCs) were successfully synthesized and incorporated into poly(lactic acid) (PLA) as a reinforcing filler to produce nanocomposite scaffolds consisting of CNC-g-PEG and PLA using an electrospinning technique. Morphological, thermal, mechanical, and wettability properties as well as preliminary biocompatibility using human mesenchymal stem cells (hMSCs) of PLA/CNC and PLA/CNC-g-PEG nanocomposite scaffolds were characterized and compared. The average diameter of the electrospun nanofibers decreased with increased filler loading level, due to the increased conductivity of the electrospun solutions. DSC results showed that both the glass transition temperature and cold crystallization temperature decreased progressively with higher CNC-g-PEG loading level, suggesting that improved interfacial adhesion between CNCs and PLA was achieved by grafting PEG onto the CNCs. Wettability of the electrospun nanofibers was not affected with the addition of CNCs or CNC-g-PEG and indicating that the fillers tended to stay inside of the fiber matrix under electrical field. The tensile strength of the composite fiber mats was effectively improved by the addition of up to 5% CNC-g-PEG up to 5wt.%. In addition, the cell culture results showed that PLA/CNC-g-PEG composite nanofibers exhibited improved biocompatibility to hMSCs, which revealed the potential application of this nanocomposite as the scaffolds in bone tissue engineering.

Multi-functional self-fluorescent unimolecular micelles for tumor-targeted drug delivery and bioimaging.

A novel type of self-fluorescent unimolecular micelle nanoparticle (NP) formed by multi-arm star amphiphilic block copolymer, Boltron® H40 (H40, a 4th generation hyperbranched polymer)-biodegradable photo-luminescent polymer (BPLP)-poly(ethylene glycol) (PEG) conjugated with cRGD peptide (i.e., H40-BPLP-PEG-cRGD) was designed, synthesized, and characterized. The hydrophobic BPLP segment was self-fluorescent, thereby making the unimolecular micelle NP self-fluorescent. cRGD peptides, which can effectively target αvß3 integrin-expressing tumor neovasculature and tumor cells, were selectively conjugated onto the surface of the micelles to offer active tumor-targeting ability. This unique self-fluorescent unimolecular micelle exhibited excellent photostability and low cytotoxicity, making it an attractive bioimaging probe for NP tracking for a variety of microscopy techniques including fluorescent microscopy, confocal laser scanning microscopy (CLSM), and two-photon microscopy. Moreover, this self-fluorescent unimolecular micelle NP also demonstrated excellent stability in aqueous solutions due to its covalent nature, high drug loading level, pH-controlled drug release, and passive and active tumor-targeting abilities, thereby making it a promising nanoplatform for targeted cancer theranostics.

Properties and fibroblast cellular response of soft and hard thermoplastic polyurethane electrospun nanofibrous scaffolds.

Soft and hard thermoplastic polyurethane (TPU) and their blends were electrospun to fabricate nanofibrous scaffolds with various properties in order to investigate the substrate property effects on cellular response. The scaffolds were characterized with Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, water contact angle tests, and protein absorption tests. It was found that the hard segment content in the scaffold increased with the hard TPU ratio, which resulted in improved hydrophobicity and decreased over all protein absorption. 3T3 fibroblasts were cultured on those scaffolds to investigate the cellular response. On soft TPU scaffolds, the cells formed were round in shape and aggregated into clusters. However, on hard TPU scaffolds, the cells exhibited a spindle shape and spread out on the scaffolds, indicating preferred cell-substrate interaction. The cell viability and proliferation of cells on hard scaffolds were higher than on soft scaffolds and on 50% hard/50% soft scaffolds.

Poly(ε-caprolactone) nanofibers with a self-induced nanohybrid shish-kebab structure mimicking collagen fibrils.

A three-dimensional structure consisting of poly(ε-caprolactone) (PCL) nanofibers covered by periodically spaced PCL crystal lamellae, a self-induced nanohybrid shish-kebab (SINSK) structure, was created using electrospinning followed by a self-induced crystallization. The resulting structure that resembles the nanotopography of natural collagen nanofibrils in the extracellular matrix (ECM) of human tissues could serve as a tissue engineering scaffold. The formation mechanism of the self-induced shish-kebab structure was investigated with real-time observation of the crystallization process. Electrospun polylactic acid (PLA)/PCL nanofibers were also employed as shish elements to study the effects of different shish materials. The results show that the geometric dimensions of the shish-kebabs are highly related to the initial concentration of PCL solution. The shish material played an important role in the creation of shish-kebab structure. Cell assays with NIH 3T3 ECACC fibroblasts suggest that the nanotopography of the nanofiber surface with kebab crystals that mimic collagen fibrils facilitated the cell attachment and spreading of 3T3 fibroblasts cells.