DEVELOPMENT OF AN ELECTROSPUN MATERIAL FOR CELL ENCAPSULATION

Background: Cell therapy has been greatly proposed as a potential therapy for many degenerative diseases. However, the therapeutic effectiveness of cell therapy is hampered by cell loss and anoikis after transplantation. Cell encapsulation by biomaterials is suggested as a useful tool to protect transplanted cell from host immune response.
Aim:
In this work, a modified microtube array membrane (MTAM) was proposed as a polymeric scaffold for cell encapsulation to prevent cell loss and matrix detachment-associated cell death. The aim was to develop improved scaffolds based on the MTAM platform using a biocompatible, degradable polymer.
Methods:
Core-shell coaxial electrospinning was utilized to fabricate MTAMs. The scaffold development was investigated using two polymers: polysulfone (PSF) and poly(lactic-co-glycolic) acid (PLGA). The MTAMs were characterized by scanning electron microscopy (SEM), goniometry, FTIR, tensile test and in vitro degradation test. The MTAMs were plasma treated and sterilized before cell loading. In this model, human dermal fibroblasts were resuspended in medium at a concentration of 1x104 cells/µl, stained with a long-term red fluorescent dye, then loaded into MTAMs by capillary force. 3D MTAMs culture were conducted under normoxic conditions and tracked using fluorescent microscopy. An in vivo biocompatibility experiment was conducted on B6 mice with five investigational groups including sham surgery alone, free PSF MTAM, free PLGA MTAM, cell-loaded version of PSF and PLGA MTAMs. After seven and 43 days of implantation, blood samples and skin tissues were harvested and analyzed.
Results:
Several new methodologies and formulations were explored. PSF and PLGA MTAMs were successfully fabricated using a core-shell electrospinning technique. SEM images revealed the structure and microfiber dimension of PSF MTAMs were around 60 x 100 µm and 35 x 90 µm in PLGA MTAMs. The scaffolds had abundant surface pores with diameters of greater than 600 nm. In vitro degradation test results showed that PSF MTAMs were highly stable in hydrated environment while PLGA degraded quickly within two months. Human dermal fibroblasts were successfully encapsulated and viable for at least 20 days in both PSF and PLGA MTAMs. Animal experiment results showed that both types of MTAM showed the ability to retain donor cells following transplantation. The results suggest that degradable PLGA MTAMs were more biocompatible than PSF MTAMs, surprisingly resulting in longer cell retention than non-degradable PSF-based materials.
Conclusion:
The microtube array membrane (MTAM) platform allows for cell encapsulation and long-term survival. PSF and PLGA MTAMs both show potential as cell delivery devices with high compatibility and cell retention. PLGA MTAMs are biodegradable which allows for non-invasive removal of the implant. However, the therapeutic efficacy of cell-loaded MTAMs is still unknown. In the future, more in vivo experiments should be conducted to study the effectiveness of encapsulated cell therapy in a specific disease models.