A naonoporous cell-therapy device with controllable biodegradation for long-term drug release

Abstract

Herein we describe the development and implementation of a nanoporous cell-therapy device with controllable biodegradation. Dopamine-secreting PC12 cells were housed within newly formulated alginate-glutamine degradable polylysine (A-GD-PLL) microcapsules. The A-GD-PLL microcapsules provided a 3-D microenvironment for good spatial cell growth, viability and proliferation. The microcapsules were subsequently placed within a poly(ethylene glycol) (PEG)-coated poly(ε-caprolactone) (PCL) chamber covered with a PEG-grafted PCL nanoporous membrane formed by phase inversion. To enhance PC12 cell growth and to assist in controlled degradation of both the PC12 cells and the device construct, small PCL capsules containing neural growth factor (PCL-NGF) and a poly(lactic-co-glycolic acid) pellet containing glutamine (PLGA-GLN) were also placed within the PCL chamber. Release of NGF from the PCL-NGF capsules facilitated cell proliferation and viability, while the controlled release of GLN from the PLGA-GLN pellet resulted in A-GD-PLL microcapsule degradation and eventual PC12 cell death following a pre-specified period of time (4 weeks in this study). In vivo, our device was found to be well tolerated and we successfully demonstrated the controlled release of dopamine over a period of four weeks. This integrated biodegradable device holds great promise for the future treatment of a variety of diseases.

Biomaterials for Personalized Cell Therapy

“…Many macrodevices consist of a cell‐loaded chamber which is separated from the host by one or more semipermeable membranes. For these membranes, PCL and polytetrafluoroethylene (PTFE)162c have been commonly used for their ability to be vascularized and apparent biocompatibility 161b,164. One promising recent design for improved immunoprotection utilizes a nanoporous PCL membrane with tightly controlled pore size 94a,161b.…”

Challenges in CRISPR/CAS9 Delivery: Potential Roles of Nonviral Vectors

“…PLL possesses a high charge density essential for effective plasmid DNA complexation and condensation. 76 In general, PLL exhibits relatively low transfection efficiency owing to lack of buffering capacity to aid in endosomal escape. 54 In order to promote the gene transfer of PLL, many PLL derivatives have been investigated.…”

Biodegradable Microcapsules Loaded with Nerve Growth Factor Enable Neurite Guidance and Synapse Formation

“…Our strategy took advantage of the previous work in which fabrication protocols, release properties, and biodegradation in situ and in vivo for the LbL-fabricated microcapsules have been established [ 12 , 23 , 24 , 33 ]. Thus, the functional data obtained here in neuronal-astrocyte co-cultures, together with the previous reports pertaining to the encapsulation per se, suggest that LbL microcapsules meet the key requirements for applications targeting brain neurons.…”

“…Although this method generates sustained endogenous production of NGF for up to a few months, it consistently showed a low cell survival rate following transplantation. An elegant innovative approach combining pharmaceutical and material sciences has been attempted, by encapsulating the NGF-secreting iPSC-derived cells, aiming to protect them from the immune response following transplantation [ 9 , 10 , 11 , 12 ]. Although the safety of this platform was confirmed, the NGF secretion level remained too low in half of the cohort [ 13 ].…”