Immobilization of hepatocytes in microcapsules has been a potentially alternative methodology for bioartificial livers (BALs). Moreover, the stability and permeability are the key parameters of these microcapsules. However, these alginate-based microcapsules are unstable if the surrounding medium disrupts the ionic interactions between alginate and the polycation. As hundreds of components are included in human plasma, the stability and permeability in plasma of microcapsules need to be sufficiently investigated. In the present study, the stability of three kinds of alginate-based microcapsules was evaluated when they were immersed in plasma. Our results showed that stability of alginate-α-poly (l-lysine)-alginate (α-APA) microcapsules was well maintained, better than those of alginate-ε-poly (l-lysine)-alginate (ε-APA) and alginate–chitosan–alginate (ACA) microcapsules. Also, factors affecting the stability of microcapsules in plasma were analyzed and it showed that heparin was the key factor that affected the stability of α-APA microcapsules, whereas heparin and low molecular electrolytes such as HCO₃⁻ and H₂PO₄⁻/HPO₄²⁻ were the factors to ε-APA and ACA microcapsules. In addition, the permeability evaluation showed no decrease in permeability of microcapsules after incubation in plasma. Our study might provide a foundation for the selection and modification of materials for microcapsule-based BAL devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2408–2416, 2014.

Cell microencapsulation is one of the promising strategies for in vitro production of proteins or in vivo delivery of therapeutic products. Membrane thickness controls microcapsule strength and permeability, which may in return affect cell growth and metabolism. In this study, the strength, permeability, and encapsulated Chinese hamster ovary cell proliferation and metabolism of four groups of microcapsules with different membrane thicknesses were investigated. It was found that increasing membrane thickness increases microcapsule strength, whereas decreases membrane permeability. During the first 6 days, cells within microcapsules with 10 μm thickness membrane proliferated fast and could reach a cell density of 1.9 × 10⁷ cells/mL microcapsule with 92% cell density. A cell density of 5.5 × 10⁷ cells/mL microcapsule with >85% cell density was achieved within microcapsules with 15 μm membrane thickness and these microcapsules kept over 88% integrity ratio after 11 days, which was much higher than that of microcapsules with 10 μm membrane thickness. Membrane with more than 20 μm thickness was not suited for encapsulated cell culture owing to low-protein diffusion rate. These results indicated that cells survived shortly within the thinnest membrane thickness. There was a specific membrane thickness more suitable for cell growth for a long-time culture. These findings will be useful for preparing microcapsules with the desired membrane thickness for microencapsulated cell culture dependent on various purposes. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

Cell microencapsulation is a promising approach for cell implantation, cell-based gene therapy, and large-scale cell culture. The well-studied α-AP (alginate–α-poly-L-lysine) microcapsules have been restricted to large-scale cell-culture and clinical applications because of high costs and cytotoxic effects in some cases. This study used ϵ-poly-L-lysine (ϵ-PLL), a high-biocompatible and low-cost food additives produced by fermentation, to prepare ϵ-AP (alginate–ϵ-PLL) microcapsules with various thickness membranes and swelling behaviors. ϵ-AP microcapsules were permeable to BSA, a standard protein of culture medium. ϵ-AP-microencapsulated Chinese hamster ovary (CHO) cells proliferated with culture time; no obvious difference with α-AP-microencapsulated CHO cells during the early 19 days. Whereas ϵ-AP-microencapsulated CHO cells kept higher viability (OD = 0.646 ± 0.012) on the 22nd day and microcapsule strength (integrity rate of 88%) on the 24th day than that of α-AP microcapsules (OD = 0.558 ± 0.025, integrity rate of 80%). ϵ-AP (alginate-ϵ-PLL) microcapsules exhibited more superior properties and could lower the costs to broaden the applications of microencapsulation technology. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

BACKGROUND: Oxygen diffusion properties affect the proliferation and metabolism of cells cultured in microcapsules with a polyelectrolyte complex membrane. The effective diffusion coefficient (De) of oxygen in alginate/chitosan (AC) microcapsules under different preparation conditions was calculated, and a mathematic model was developed to investigate the effect of oxygen diffusion on cell loading in the microcapsules.

RESULTS: Oxygen De in AC microcapsules was independent of alginate solution concentration, intrinsic viscosity of alginate and different polyelectrolyte complex membranes. De decreased from 2.1 ± 0.3 × 10⁻⁹ to 0.17 ± 0.01 × 10⁻⁹ m² s⁻¹ as microcapsule diameter decreased from 1800 to 45 0 µm. Microcapsule density was increased from 1.013 ± 0.000 to 1.034 ± 0.003 g mL⁻¹ as diameter decreased from 1775 to 430 µm. The mathematic model results showed that critical CHO cell loadings were 1.8 × 10⁸ or 1.1 × 10⁸ cells mL⁻¹ in microcapsules with 450 or 1800 µm diameter, respectively.

CONCLUSIONS: No significant difference was found of oxygen De between calcium alginate beads and AC microcapsules. The decrease of De with diameter was attributed to the increasing density and compact degree on the surface. The model results indicated that risk on necrosis rose with the increasing diameter. Microcapsules with smaller diameters may have more advantages on cell culture. © 2012 Society of Chemical Industry

Edible starch sodium octenyl succinate (SSOS) films, with or without glycerol as plasticizer, were prepared by solution-casting method. The effect of SSOS concentration, degree of substitution (DS) of octenyl group, as well as glycerol content, on the properties of SSOS films was studied including tensile strength, water vapor permeability (WVP), and oil permeability (OP). The results indicated that the tensile strength of SSOS film was up to 39.4 ± 1.9 MPa when the concentration of SSOS was 0.05 g/mL and DS was 0.05. The increase of glycerol content resulted in a decrease of film tensile strength. WVP of SSOS films was relatively low. Meanwhile, study in OP showed that SSOS films were oilproof. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

Microencapsulation has been a promising approach for drug delivery, cell implantation, cell-based gene therapy and large-scale cell culture. To make use of microcapsules more effectively, it is important to accurately construct the microcapsule membranes with desired properties including a certain thickness, strength, and so forth. To date single factor experiments have been widely used, however, they are time-consuming to obtain the desired membrane preparation conditions. Response surface methodology (RSM) is a mathematical and statistical technique for building empirical models that gained importance for optimizing reacting conditions. In this study, three signifficant effect factors that affect alginate-based microcapsule membrane properties, including membrane thickness, swelling degree, and mechanical stability, were determined with Plackett–Burman method, and then three empirical models were built to optimize the preparation conditions of the microcapsule membranes according to the responses of these three signifficant effect factors respectively with RSM. These models can be used to predict the characteristics of microcapsules under different membrane preparation conditions, which provide a guide for optimizing the microencapsulation technology. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Alginate-chitosan-alginate (ACA) microcapsules have been developed as a device for the transplantation of living cells. However, protein adsorption onto the surface of microcapsules immediately upon their implantation decides their ultimate biocompatibility. In this work, the chemical composition of the ACA membranes was determined using X-ray photoelectron spectroscopy (XPS). The surface wettability and charge were determined by contact angle and zeta potential measurements, respectively. Then, the effects of surface wettability and charge on bovine fibrinogen (Fgn) and gamma globulin (IgG) adsorption onto ACA microcapsules were evaluated. The results showed that ACA microcapsules had a hydrophilic membrane. So, the surface wettability of ACA microcapsules had little effect on protein adsorption. There was a negative zeta potential of ACA microcapsules which varies with the viscosity or G content of alginate used, indicating a varying degree of net negatively charged groups on the surface of ACA microcapsules. The amount of adsorbed protein increased with increasing of positive charge. Furthermore, the interaction between proteins and ACA microcapsules is dominated by electrostatic repulsion at pH 7.4 and that is of electrostatic attraction at pH 6.0. This work could help to explain the bioincompatibility of ACA microcapsules and will play an important role in the optimization of the microcapsule design. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010

Alginate/chitosan polyelectrolyte complex (PEC) hybrid fibers are promising materials for scaffold-making in tissue engineering. In this study, a new method termed “hydro-spinning” was developed to make alginate/chitosan hybrid fibers. In hydro-spinning, a chitosan solution was pumped into a flowing sodium alginate solution and sheared into streamlines. These elongated streamlines subsequently transformed into alginate/chitosan PEC ribbon-like fibers before breaking up into pieces. Average diameter and chitosan content of the fibers correlated positively with the chitosan concentration used in spinning. These hybrid fibers showed a high water-absorbability of around 50-fold to 60-fold of water to their dry weight and could retain their integrity after saturation in minimum essential medium (MEM) medium for 30 days. In vitro culture experiments demonstrated that these fibers were able to support the three-dimensional growth of MCF-7, suggesting the potential applications of these fibers in biomedical and bioengineering fields such as tissue engineering. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010

Microencapsulation of recombinant cells is a novel means for gene therapy. However, one of the major concerns is the relationship between the permeability of microcapsule and cell growth. Many studies have focused on the permeability of empty microcapsule, but little is known about the effect of the cell growth on the permeability of a cell-contained microcapsule. A combination of fluorescence labeled protein and confocal laser scanning microscope (CLSM) provides the information about the permeability changes during the cell growth. A decrease of membrane permeability was detected on the 14th day. Meanwhile, membrane surface protein fouling was also investigated. A significant increase of membrane surface protein content was detected on the 21st day. In order to study the effect of the permeability changes on the cell viability, the membrane of cell-contained microcapsules with different permeability was set up by incubating gel beads in poly-L-lysine for 5 and 30 min, respectively, to mimic the bovine serum albumin cutoff, and a retard of cell growth was found in 7 days' culture. These results showed that the protein fouling of the microcapsule membrane caused by the cell growth may be an important factor to influence cell viability. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009

Microencapsulation of recombinant cells secreting endostatin offers a promising approach to tumor gene therapy in which therapeutic protein is delivered in a sustainable and long-term fashion by encapsulated recombinant cells. However, the studies of cell growth and protein production in vivo are very limited. In this study, the effects of microencapsulation parameters on in vivo cell growth, endostatin production, and microcapsule stability after implantation in the peritoneal cavity of mice were for the first time investigated. Microcapsules with liquid core reached higher cell density and endostatin production at day 18 than microcapsules with solid core. There was no significant difference in stability whether the core of the microcapsule was solid or liquid. Decrease in microcapsule size increased the stability of microcapsule. The microcapsules kept intact in the peritoneal cavity of mice after 36 days of implantation when the microcapsules size was 240 μm in diameter, which gave rise to high endostatin production as well. The optimized microencapsulation conditions for in vivo implantation are liquid core and 240 μm in diameter. This study provides useful information for antiangiogenic gene therapy to tumors using microencapsulated recombinant cells. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008