Thursday, February 25, 2010

Microencapsulation for Cell Delivery

Microencapsulation is currently the most widely used form of cell delivery with preparation methods including:

1. Gelation and polyelectrolyte complexation,
2. Interfacial polymerization/phase inversion and
3. Conformal coating.

Microencapsulation involves surrounding a collection of cells with a thin generally micrometer sized, semipermeable membrane. Its primary purpose is to protect the encapsulated cells from the host’s immune system, while allowing the exchange of small molecules and thereby ensuring cell survival and function. There are several requirements for polymer capsules or hydrogels used as components of microcapsules:

# Noncytotoxicity to the encapsulated cells

# Biocompatibility with the surrounding environment where capsules are to be implanted (e.g., minimal fibrotic response)

# Adequate permeability for diffusion of essential nutrients (e.g., oxygen and glucose for islets of Langerhans) and cell secretory products (such as insulin, metabolic waste)

# Impermeability to secreted antibodies of the host’s immune system (e.g., immunoglobulins and glycoproteins after complement activation

# Chemical and mechanical stability

From the technological point of view, the requirements for microencapsulation include:

# Small capsule diameters to ensure sufficient diffusion and internal organ transplantability (depending on application, < 400 μm for bioartificial pancreas), with the cell centering within the microcapsule

# Minimum shrinking/swelling due to changes in osmotic conditions upon transplantation

# Uniform wall thickness for optimum transport of molecules across the membrane and effective immunoprotection.

In addition, the technology used for encapsulation must be nontraumatic to the encapsulated cells. This includes minimizing the mechanical stress during encapsulation and solvent toxicity (if any), as well as optimizing temperature, viscosity, pH and ionic strength. This, in turn, limits the concentration and molecular mass which can be employed. In addition, the ionic content of the polymer backbone (density distribution of charges in the polymer chain), the chemistry and location of functional group attachment, the chain rigidity, aromaticity, conformation and extent of branching were identified as important variables in the type of complex produced. The presence of secondary hydrogen bonding interactions was also found to be significant.

Several problems may prevent wide scale application of microcapsules in the clinic. The capsules can clump together, in which case the cells towards the center may suffer severely from limited diffusion of oxygen and nutrients. A substantial fraction of the capsules may also adhere to tissue. If the capsules degrade, the liberated islet cells, even if nonviable, would greatly increase the antigenic burden on the patient. Semipermeable polymeric membranes have been developed with the aim of permitting the transplantation of xenogenic cells thus removing the need for immunosuppression therapy. However, early clinical implementations is not likely to involve xenografts or genetically modified cells but rather auto- and allografts supplemented by immunosuppression when necessary.

Tags: Bio Technology, Bio Genetics, Cell Encapsulation

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