Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.

Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell-secreted biomolecules. However, fibrotic tissue deposition around the device has been shown to compromise the long-term function of the transplanted cells. Herein, a macroencapsulation device design that improves long-term survival and function of the transplanted cells is reported. The device is comprised of a semipermeable chitosan pouch with a tunable reservoir and molecularly engineered interface. The chitosan pouch interface decorated with 1,12-dodecanedioic acid (DDA), limits the cell adhesion and vigorous foreign body response while maintaining the barrier properties amenable to cell encapsulation. The device provides long-term protection to the encapsulated human primary hepatocytes in the subcutaneous space of immunocompetent mice. The device supports the encapsulated cells for up to 6 months as evident from cell viability and presence of human specific albumin in circulation. Solutions that integrate biomaterials and interfacial engineering such as the one described here may advance development of easy-to manufacture and retrievable devices for the transplantation of therapeutic cells in the absence of immunosuppression.

Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.

BACKGROUND: Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest approaches that attempted to deliver hepatocytes via portal vein or spleen achieved little success due to poor engraftment. More recent efforts include transplantation of cell sheets or thin hepatocyte-laden synthetic hydrogels. However, these implants must remain sufficiently thin to ensure that nutrients can diffuse into the implant. METHODS: To circumvent these limitations, we investigated the use of a vascularizable dual-compartment hydrogel system for minimally invasive transplantation of primary hepatocytes. The dual-compartment system features a macroporous outer polyethylene glycol diacrylate/hyaluronic acid methacrylate hydrogel compartment for seeding supportive cells and facilitating host cell infiltration and vascularization and a hollow inner core to house the primary human hepatocytes. RESULTS: We show that the subcutaneous implantation of these cell-loaded devices in NOD/SCID mice facilitated vascular formation while supporting viability of the transplanted cells. Furthermore, the presence of human serum albumin in peripheral blood and the immunostaining of excised implants indicated that the hepatocytes maintained function in vivo for at least 1 month, the longest assayed time point. CONCLUSIONS: Cell transplantation devices that assist the anastomosis of grafts with the host can be potentially used as a minimally invasive ectopic liver accessory to augment liver-specific functions as well as potentially treat various pathologies associated with compromised functions of liver, such as hemophilia B or alpha-1 antitrypsin deficiency.

Biomaterials for pluripotent stem cell engineering: From fate determination to vascularization.

Recent advancements in material science and engineering may hold the key to overcoming reproducibility and scalability limitations currently hindering the clinical translation of stem cell therapies. Biomaterial assisted differentiation commitment of stem cells and modulation of their in vivo function could have significant impact in stem cell-centred regenerative medicine approaches and next gen technological platforms. Synthetic biomaterials are of particular interest as they provide a consistent, chemically defined, and tunable way of mimicking the physical and chemical properties of the natural tissue or cell environment. Combining emerging biomaterial and biofabrication advancements may finally give researchers the tools to modulate spatiotemporal complexity and engineer more hierarchically complex, physiologically relevant tissue mimics. In this review we highlight recent research advancements in biomaterial assisted pluripotent stem cell (PSC) expansion and three dimensional (3D) tissue formation strategies. Furthermore, since vascularization is a major challenge affecting the in vivo function of engineered tissues, we discuss recent developments in vascularization strategies and assess their ability to produce perfusable and functional vasculature that can be integrated with the host tissue.