title: Hybrid scaffold composed of hydrogel/3D-framework and its application as a dopamine delivery system.
abstract: Cell-based drug delivery systems (DDSs) have been increasingly exploited because cells can be utilized as a continuous drug delivering system to produce therapeutic molecules over a more extended period compared to the simple drug carriers. Although hydrogels have many advantages for this application, their mechanical properties are generally not desirable to structurally protect implanted cells. Here, we present a three-dimensional (3D) hybrid scaffold with a combination of a 3D framework and a hydrogel to enhance the mechanical properties without chemically altering the transport properties of the hydrogel. Based on the 3D Ormocomp scaffold (framework) fabricated by projection-based microstereolithography with defined parameters, we developed a 3D hybrid scaffold by injection of the mixture of cells and the alginate gel into the internal space of the framework. This hybrid scaffold showed the improved mechanical strength and the framework in the scaffold played the role of an adhesion site for the encapsulated cells during the culture period. Additionally, we confirmed its protection of exogenous human cells from acute immune rejection in a mouse model. Eventually, we demonstrated the feasibility of applying this hybrid scaffold to the treatment of Parkinson's disease as a cell-based DDS. Dopamine released from the 3D hybrid scaffolds encapsulating dopamine-secreting cells for 8weeks suggested its clinical applicability. Further study on its long-term efficacy is necessary for the clinical applicability of this 3D hybrid scaffold for the treatment of Parkinson's disease.
authors: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors: Kyung Shin
authors: KS
authors: Kang
authors: Agency for Defense Development, Daejeon 305-152, South Korea.
authors: Soo-In
authors: SI
authors: Lee
authors: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors: Jung Min
authors: JM
authors: Hong
authors: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors: Jin Woo
authors: JW
authors: Lee
authors: Department of Neurosurgery, Seoul National University Hospital, Seoul 110-774, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-774, South Korea.
authors: Hwa Yeon
authors: HY
authors: Cho
authors: Department of Brain and Cognitive Science, Ewha Womans University, Seoul 120-750, South Korea.
authors: Jin H
authors: JH
authors: Son
authors: Department of Neurosurgery, Seoul National University Hospital, Seoul 110-774, South Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, South Korea; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-774, South Korea. Electronic address: paeksh@snu.ac.kr.
authors: Sun Ha
authors: SH
authors: Paek
authors: Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang 790-784, South Korea. Electronic address: dwcho@postech.ac.kr.
authors: Dong-Woo
authors: DW
authors: Cho
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000008:administration & dosage*; D015259:Dopamine Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000188:drug therapy; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D015259:Dopamine Agents; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D004298:Dopamine
keywords: Dopamine; Drug delivery system; Hydrogel; Parkinson's disease; Scaffold