Macro-capsule Fabrication via 3D printing for Cellular Therapy 3B basım ile üretilen makro kapsülün hücresel tedavide kullanımı

Purpose: Cell transplantation is a widely used method to induce cell-mediated immune reactions inside the body. However, possible immune responses to the transplanted cells decrease the efficiency of applied cell therapy. This issue can be addressed by the transplantation of cells via 3D-printed polymeric capsules which encapsulate cells and protect them from immune system attacks. Cell-loaded capsules (macro or micro) have emerged as potential carriers for more efficacious cellular therapies. In this study, 3D-printed porous capsules were prepared from biodegradable and biocompatible polyester “polycaprolactone (PCL)” and this macro-capsule was evaluated as a carrier for its cell encapsulation effectiveness. Method: The macro-capsule was designed to have dimensions of 2x5x10 mm and drawn in Autodesk Fusion 360 program. PCL was utilized for its 3D bio-printing via Axolotl Bioprinter Dual Print Head System. Leakage on the closed form of the macro-capsule was visually controlled by surface electron microscopy (SEM). Permeability of the macro-capsule was tested with trypan blue dye and human serum albumin (HSA) protein. Sterilization of the obtained macro-capsule was achieved via UV light and the cytotoxicity of the polycaprolactone capsule was tested for 24 and 72 hour incubation time periods. Results: The semi-permeable macro-capsule was successfully obtained as closed and hollow form. Its porous structure was demonstrated using trypan blue dye. To evaluate the porosity of the macrocapsule, human serum albumin (HSA) protein release was performed from the macrocapsule. It has been shown that 98% of HSA was released from the macrocapsule within 24 hours. The polycaprolactone (PCL) macrocapsule was sterilized using UV light and was reported to show no in vitro cytotoxicity. In addition, it was shown that the cells in the macro-capsule consumed at least 10% glucose from the outside medium during 12 days of incubation, compared to 2D cell culture conditions, and were able to release at least 8% of the lactic acid molecules outside. Conclusion: In conclusion, reproducible fabrication of polymer macro-capsule, high viability of encapsulated cells inside, and their metabolic assessment results have obviously indicated the potential of these capsules as effective carriers for living cells with transplantation-dependent cellular therapies.