Design of artificial red blood cells using polymeric hydrogel microcapsules: hydrogel stability improvement and polymer selection.

PURPOSE: To improve the stability of pectin-oligochitosan hydrogel microcapsules under physiological conditions. METHODS: Two different approaches were examined: change of the cross-linker length and treatment of the hydrogel microcapsules with 150 Mm CaCl2. Replacement of pectin with alginate was also studied. RESULTS AND CONCLUSIONS: It was observed that the molecular weight of the cross-linker oligochiotsan had no significant improvement on microcapsule stability. On the other hand, the treatment of pectin-oligochitosan microcapsules with Ca2+ increased the microcapsule stability significantly. Different types of alginate were used; however, no red-blood-cell-shaped microcapsules could be produced, which is likely due to the charge-density difference between deprotonated pectin and alginate polymers.

Novel pectin-based carriers for colonic drug delivery.

Pectin-based hydrogel carriers have been studied and shown to have promising applications for drug delivery to the lower GI tract, especially to the colonic region. However, making sure these hydrogel carriers can pass through the upper GI tract and reach the targeted regions, after oral administration, still remains a challenge to overcome. A solution to this problem is to promote stronger cross-linking interactions within the pectin-based hydrogel network. The combined usage of a divalent cation (Ca(2+)) and the cationic biopolymer oligochitosan has shown to improve the stability of pectin-based hydrogel systems - suggesting that these two cross-linkers may be used to eventually help improve pectin-based hydrogel systems for colonic drug delivery methods.

Development of a microscale red blood cell-shaped pectin-oligochitosan hydrogel system using an electrospray-vibration method: preparation and characterization.

PURPOSE: To develop and characterize a microscale pectin-oligochitosan hydrogel microcapsule system that could be applied in such biological fields as drug delivery, cell immobilization/encapsulation, and tissue engineering. METHODS: Microscale pectin-oligochitosan hydrogel microcapsules were prepared by using the vibration/electrostatic spray method. The morphology and chemistry of the hydrogel microcapsules were characterized by using scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR), respectively. The designed hydrogel microcapsule system was then used to study the responsiveness of the microcapsules to different simulated human body fluids as well as cell encapsulation. RESULTS: The designed hydrogel microcapsule system exhibited a large surface area-to-volume ratio (red blood cell-shaped) and great pH/enzymatic responsiveness. In addition, this system showed the potential for controlled drug delivery and three-dimensional cell culture. CONCLUSION: This system showed a significant potential not only for bioactive-agent delivery, especially to the lower gastrointestinal (GI) tract, but also as a three-dimensional niche for cell culture. In particular, the hydrogel microcapsule system could be used to create artificial red-blood-cells as well as blood substitutes.

A model of venous return while utilizing vacuum assist during cardiopulmonary bypass.

In order for vacuum-assisted venous return (VAVR) to be used safely and efficiently during cardiopulmonary bypass (CPB), a full understanding of venous return is necessary. The focus of this work was to use the concepts of energy conservation and viscous energy dissipation in the development of a theoretical model of venous return utilizing vacuum assist. The effectiveness and accuracy of this model has been verified through in vitro laboratory investigations and statistical analysis. Although VAVR can provide higher flows through smaller venous cannula, vacuum assist may lead to increased levels of wall shear stress as shown in this work. The clinical implications of VAVR have yet to be investigated, but may lead to an exacerbation of the detrimental effects of CPB during cardiac surgery.

A review of leukofiltration in cardiac surgery: the time course of reperfusion injury may facilitate study design of anti-inflammatory effects.

The systemic inflammatory response syndrome (SIRS) is a well-recognized phenomenon attending cardiopulmonary bypass (CPB) surgery. SIRS leads to costly complications and several strategies intended to ameliorate the symptoms have been studied, including leukocyte reduction using filtration. Although the body of work suggests that leukoreduction attenuates SIRS, discrepancies remain within the literature. The recent literature is reviewed, highlighting the areas where concordance is lacking. Investigations into many promising device-related technologies are often deterred by the high costs of clinical trials. Adding to costs is the fact that clinical end points generally require large sample sizes. An understanding, however, of the pathogenesis of reperfusion injury can guide the investigator to choose physiologic response measures that correlate well with clinical outcome, but feature low inherent variability, allowing for clinical trials with smaller sample sizes. With this goal in mind, a model for the pathogenesis of reperfusion injury is described. Using a model of reperfusion injury as underpinnings for the design of prospective pilot studies, we show that salvaged blood reinfused following CPB elicits time-dependent effects on pulmonary function as predicted by the model. Data are illustrative of principles that could expand the scope of clinical investigations designed to validate the use of physiologic response measures as correlates of clinical outcome. Such investigations would target surrogate markers of clinical outcome, measured at clinically relevant times. Once validated, these surrogate markers would, thereafter, become economical screening tools for clinical studies of device-related or pharmacological anti- inflammatory interventions.