TY - JOUR
T1 - Transcutaneously refillable, 3D-printed biopolymeric encapsulation system for the transplantation of endocrine cells
AU - Farina, Marco
AU - Chua, Corrine Ying Xuan
AU - Ballerini, Andrea
AU - Thekkedath, Usha
AU - Alexander, Jenolyn F.
AU - Rhudy, Jessica R.
AU - Torchio, Gianluca
AU - Fraga, Daniel
AU - Pathak, Ravi R.
AU - Villanueva, Mariana
AU - Shin, Crystal S.
AU - Niles, Jean A.
AU - Sesana, Raffaella
AU - Demarchi, Danilo
AU - Sikora, Andrew G.
AU - Acharya, Ghanashyam S.
AU - Gaber, A. Osama
AU - Nichols, Joan E.
AU - Grattoni, Alessandro
N1 - Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/9
Y1 - 2018/9
N2 - Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention and survival. Cell transplant success requires homing to vascularized environment, cell engraftment and importantly, maintenance of inherent cell function. To address this need, we developed a three dimensional (3D) printed cell encapsulation device created with polylactic acid (PLA), termed neovascularized implantable cell homing and encapsulation (NICHE). In this paper, we present the development and systematic evaluation of the NICHE in vitro, and the in vivo validation with encapsulated testosterone-secreting Leydig cells in Rag1−/− castrated mice. Enhanced subcutaneous vascularization of NICHE via platelet-rich plasma (PRP) hydrogel coating and filling was demonstrated in vivo via a chorioallantoic membrane (CAM) assay as well as in mice. After establishment of a pre-vascularized bed within the NICHE, transcutaneously transplanted Leydig cells, maintained viability and robust testosterone secretion for the duration of the study. Immunohistochemical analysis revealed extensive Leydig cell colonization in the NICHE. Furthermore, transplanted cells achieved physiologic testosterone levels in castrated mice. The promising results provide a proof of concept for the NICHE as a viable platform technology for autologous cell transplantation for the treatment of a variety of diseases.
AB - Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention and survival. Cell transplant success requires homing to vascularized environment, cell engraftment and importantly, maintenance of inherent cell function. To address this need, we developed a three dimensional (3D) printed cell encapsulation device created with polylactic acid (PLA), termed neovascularized implantable cell homing and encapsulation (NICHE). In this paper, we present the development and systematic evaluation of the NICHE in vitro, and the in vivo validation with encapsulated testosterone-secreting Leydig cells in Rag1−/− castrated mice. Enhanced subcutaneous vascularization of NICHE via platelet-rich plasma (PRP) hydrogel coating and filling was demonstrated in vivo via a chorioallantoic membrane (CAM) assay as well as in mice. After establishment of a pre-vascularized bed within the NICHE, transcutaneously transplanted Leydig cells, maintained viability and robust testosterone secretion for the duration of the study. Immunohistochemical analysis revealed extensive Leydig cell colonization in the NICHE. Furthermore, transplanted cells achieved physiologic testosterone levels in castrated mice. The promising results provide a proof of concept for the NICHE as a viable platform technology for autologous cell transplantation for the treatment of a variety of diseases.
KW - 3D printing
KW - Cell transplantation
KW - Leydig cells
KW - Pancreatic islets
KW - Subcutaneous implant
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U2 - 10.1016/j.biomaterials.2018.05.047
DO - 10.1016/j.biomaterials.2018.05.047
M3 - Article
C2 - 29886385
AN - SCOPUS:85049354315
SN - 0142-9612
VL - 177
SP - 125
EP - 138
JO - Biomaterials
JF - Biomaterials
ER -