Biodegradable sponges for hepatocyte transplantation

Abstract

Liver cell transplantation may provide a means to replace lost or deficient liver tissue, but devices capable of delivering hepatocytes to a desirable anatomic location and guiding the development of a new tissue from these cells and the host tissue are needed. We have investigated whether sponges fabricated from poly-L-lactic acid (PLA) infiltrated with polyvinyl alcohol (PVA) would meet these requirements. Highly porous sponges (porosity = 90-95%) were fabricated from PLA using a particulate leaching technique. To enable even and efficient cell seeding, the devices were infiltrated with the hydrophilic polymer polyvinyl alcohol (PVA). This reduced their contact angle with water from 79 to 23 degrees, but did not inhibit the ability of hepatocytes to adhere to the polymer. Porous sponges of PLA infiltrated with PVA readily absorbed aqueous solutions into 98% of their pore volume, and could be evenly seeded with high densities (5 x 10(7) cells/mL) of hepatocytes. Hepatocyte-seeded devices were implanted into the mesentery of laboratory rats, and 6 +/- 2 x 10(5) of the hepatocytes engrafted per sponge. Fibrovascular tissue invaded through the devices' pores, leading to a composite tissue consisting of hepatocytes, blood vessels and fibrous tissue, and the polymer sponge.

Morphological and Functional Changes of Rat Hepatocytes by Vertical Cell-Cell Adhesion in Three-Dimensional Stacked-Up Culture

“…Although several 3D-culture methods were developed to maintain hepatocyte function (4)(5)(6)(7)(8)(9) , it was difficult to monitor 3D cellular morphology with a high optical resolution because of the large tissue scales. In particular, how cells change their shape and function when the culture condition changes from 2D-to 3D-configurations remains elusive.…”

“…Several 3D culture methods have been developed to mimic the 3D microenvironment that is important for maintaining hepatocyte functions in vitro. Hepatocytes were cultured in a 3D-configuration using microreactors (4,5) , biodegradable scaffolds (6,7) , and the spheroid-culture methods (8,9) . In 3D microenvironments, hepatocytes maintain their differentiated functions such as albumin secretion and urea synthesis.…”

The modern creation technologies of implanted bioartificial liver

“…При таком ко-культивировании на 3D-матриксах клетки сохраняли свою функциональную активность вплоть до 6 месяцев in vivo [20][21][22][23]. Гепатоциты успешно культивировали на поли-молочной кислоте (PLA) [64], поли-гликолевой кислоте (PGA) [66] и их сополимерах [12,65,67].Zavan B. c соавт.[69] сообщили о возможностях нетканых губчатых материалов на основе гиалурановых природных соединений (бензиловый эфир гиалурановой кислоты -HYAFF-11 FAB-Italy) для культивирования гепатоцитов и бета-клеток крысы in vitro. Сравнивали результаты, полученные в присутствии экстрацеллюлярного матрикса, создаваемого фибробластами, предварительно культивированными в подложку, и на полной среде без фибробластов.…”

“…При таком ко-культивировании на 3D-матриксах клетки сохраняли свою функциональную активность вплоть до 6 месяцев in vivo [20][21][22][23]. Гепатоциты успешно культивировали на поли-молочной кислоте (PLA) [64], поли-гликолевой кислоте (PGA) [66] и их сополимерах [12,65,67].…”

Advances in bioartificial liver devices

“…12 Alternatives to whole organ transplantation for liver dysfunction are under active investigation. Figure 1 schematically depicts the 4 main cellular approaches that are currently being investigated: isolated cell transplantation, [13][14][15][16][17] tissue engineering of implantable constructs, [18][19][20][21][22][23][24][25][26][27] transgenic xenotransplantation, [28][29][30][31] and extracorporeal bioartificial liver devices (BAL). Extracorporeal support for patients suffering from liver failure has been attempted for over 40 years.…”