ABSTRACT
Right ventricular outflow tract (RVOT) reconstruction is a common surgical method to treat congenital cardiac lesions, and bovine jugular vein conduit (BJVC) has become a prevalent candidate of prosthetic material for this procedure since 1999. Although many clinical studies have shown encouraging results on BJVCs, complications such as stenosis, aneurysmal dilatation, valve insufficiency, and infective endocarditis revealed in other clinical outcomes still remain problematic. This review describes the underlying mechanisms causing respective complications, and summarizes the current technological development that may address those causative factors. Novel crosslinking agents, decellularization techniques, conduit coatings, and physical reinforcement materials have improved the performances of BJVCs. The authors expect that the breakthroughs in the clinical application of BJVC may come from new genetic research findings and advanced characterization apparatuses and bioreactors, and are optimistic that the BJVC will in the future provide sophisticated therapies for next-generation RVOT reconstruction.
ABSTRACT
This study reports the encapsulation of vancomycin, as a model hydrophilic drug, into poly(lactide-co-glycolide) microspheres using a novel reformative shear precipitation procedure. In contrast to the external aqueous phase used in the conventional microencapsulation technique based on emulsion solvent evaporation/extraction, the reformative shear precipitation procedure explored in this study uses a shear medium composed of glycerol as the viscous medium and ethanol as polymer antisolvent, which is relatively immiscible with the hydrophilic drug. This limits drug diffusion and leads to rapid microsphere solidification, which allows a large proportion of the hydrophilic drug to be encapsulated within the microspheres. The influence of various processing parameters, including polymer concentration, volume ratio of ethanol to glycerol in the shear medium, volume of aqueous drug solution, initial drug loading, and injecting rate of the drug-polymer emulsion, on the encapsulation efficiency and characteristics of resulting microspheres were investigated. The morphology and release characteristics, as well as mechanical, in vitro and in vivo behaviour of vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using the novel procedure were also investigated. The results demonstrated that the reformative shear precipitation procedure could achieve the loading of hydrophilic drugs into poly(lactide-co-glycolide) microspheres with high encapsulation efficiency, and the success of the procedure was largely influenced by the volume ratio of ethanol to glycerol in the shear medium. Vancomycin-loaded poly(lactide-co-glycolide) microspheres prepared using this procedure demonstrated favourable mechanical characteristics, antibacterial activity, and in vivo degradation behaviour which suggested their suitability for use as a sustained delivery system.
Subject(s)
Capsules/chemical synthesis , Fractional Precipitation/methods , Polyglactin 910/chemistry , Staphylococcus aureus/drug effects , Vancomycin/administration & dosage , Vancomycin/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Capsules/administration & dosage , Cell Survival/drug effects , Cell Survival/physiology , Compressive Strength , Diffusion , Drug Compounding/methods , Hydrophobic and Hydrophilic Interactions , Shear Strength , Staphylococcus aureus/cytology , Staphylococcus aureus/physiologyABSTRACT
The extent of substrate stiffness has been shown to be predominant in regulating cellular behaviors. Previous studies have used matrices such as elastomers or hydrogels to understand cell behavior. Herein, liquid crystalline matrices that resemble movable morphology of biomembrane and viscoelasticity were fabricated with tunable storage modulus for the evaluation of the modulus-driven cell behaviors. Our results demonstrated that NIH/3T3 cells showed a hypersensitive response to the storage modulus of liquid crystalline substrates by the alteration in attachment, spreading, proliferation and viability, polarization, cell cycle and apoptosis, and activity of mechano-transduction-related signal molecules including FAK, paxillin and ERK. The octyl hydroxypropyl cellulose substrates (OPC-1-5) with intermediate storage modulus of 12,312Pa and 7228Pa (OPC-2 and OPC-3 respectively) could provide more beneficial adhesion conditions leading to a larger spreading area, more elongated morphology and higher proliferation rates possibly through paxillin-ERK pathway, whereas the substrates with the highest or lowest storage modulus (16,723Pa, OPC-1; and 41Pa, OPC-5, respectively) appeared unfavorable for cell growth. Our study provides insights into the mechanism of modulus-driven cellular behaviors for better design of bioengineered cell substrates.
