Small (~100 µm ) microcapsules for cell micro encapsulation


Reference #: 00892


Alginate is one of the most widely used biomaterials for cell microencapsulation due to its natural origin and excellent biocompatibility. Alginate microcapsules can be coated with a polycation layer to increase stability and allow for further control of membrane permeability of the microcapsules. Poly-L-lysine (PLL) is the most studied and utilized polycation to produce alginate-PLL-alginate (APA) microcapsules. However, PLL induces cytokine production in monocytes and can cause cellular necrosis. Chitosan has attracted much attention as a replacement for PLL. Chitosan is less immunogenic than PLL and has excellent cell affinity. Chitosan has been applied for microencapsulation of various mammalian cells. However, processes involved with high molecular weight chitosan must be carried out at pH levels much lower than that required for mammalian cell survival. Moreover, the chitosan coating process requires a relatively long coating time. This prolonged exposure of mammalian cells to the undesired low pH results in low cell viability after coating. These difficulties may explain why no study has been reported to succesfully synthesize ACA (alginate-chitosan-alginate) microcapsules for cell microencapsulation. In a previous study, Dr. He’s research team successfully encapsulated cells in small (~ 100 µm) alginate microspheres with high cell viability using the electrostatic spray method.

Invention Description:

In the present study, the small microspheres were further coated with low molecular weight chitosan and then alginate to produce ACA microspheres. The core of the microspheres was further liquefied to obtain ACA microcapsules. Dr. He’s research team successfully achieved chitosan coating of small (~ 100 µm) cell-loaded ACA microcapsules with great immediate cell viability (> ~ 95%). The membranes of the microcapsules were found to be selectively permeable. More importantly, the encapsulated cells were shown to survive well during a one-month-long extended culture. Therefore, the small ACA microcapsule is a promising system to encapsulate non-autologous cells for the emerging cell-based medicine.

Potential Applications:

Transplantation of encapsulated cells has been proposed to be a promising method for the treatment of a wide variety of diseases such as diabetes, metabolic deficiencies, liver failure, and Parkinson's disease. Additionally, microencapsulated recombinant cells have been used for gene therapy of bone defects and treatment of neurodegenerative and cardiovascular diseases.

Advantages and Benefits:

Small microcapsules offer numerous advantages over larger microcapsules, including:

  1. Reduction in microcapsule size promotes the molecular exchange between the encapsulated cells and their surrounding environment. In particular, size reduction reduces the resistance to the transport of oxygen and nutrients to the encapsulated cells and enhances transfer of therapeutic products secreted by the cells out of the capsule

  2. Small microcapsules have been shown to have better mechanical stability and biocompatibility

  3. Reduction in microcapsule size suppresses foreign body response to implanted microcapsules

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
Microcapsules for Cell Microencapsulation Utility United States 13/416,563 3/9/2012      
For Information, Contact:
Technology Commercialization
University of South Carolina
Xiaoming He
Wujie Zhang
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