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Berkeley, CA, United States

Wang A.,University of California at Berkeley | Tang Z.,University of California at Berkeley | Park I.-H.,Dana-Farber Cancer Institute | Park I.-H.,Brigham and Womens Hospital | And 10 more authors.
Biomaterials | Year: 2011

Induced pluripotent stem cells (iPSCs) hold great promise for cell therapies and tissue engineering. Neural crest stem cells (NCSCs) are multipotent and represent a valuable system to investigate iPSC differentiation and therapeutic potential. Here we derived NCSCs from human iPSCs and embryonic stem cells (ESCs), and investigated the potential of NCSCs for neural tissue engineering. The differentiation of iPSCs and the expansion of derived NCSCs varied in different cell lines, but all NCSC lines were capable of differentiating into mesodermal and ectodermal lineages, including neural cells. Tissue-engineered nerve conduits were fabricated by seeding NCSCs into nanofibrous tubular scaffolds, and used as a bridge for transected sciatic nerves in a rat model. Electrophysiological analysis showed that only NCSC-engrafted nerve conduits resulted in an accelerated regeneration of sciatic nerves at 1 month. Histological analysis demonstrated that NCSC transplantation promoted axonal myelination. Furthermore, NCSCs differentiated into Schwann cells and were integrated into the myelin sheath around axons. No teratoma formation was observed for up to 1 year after NCSC transplantation in vivo. This study demonstrates that iPSC-derived multipotent NCSCs can be directly used for tissue engineering and that the approach that combines stem cells and scaffolds has tremendous potential for regenerative medicine applications. © 2011 Elsevier Ltd.

Jin J.,San Francisco Medical Center | Jin J.,University of California at San Francisco | Park M.,San Francisco Medical Center | Park M.,University of California at San Francisco | And 13 more authors.
Regenerative Medicine | Year: 2012

Aim: Current synthetic tubular conduits are inferior to nerve autograft for the repair of segmental peripheral nerve injuries. We examined motor outcomes with the use of longitudinally aligned poly (L-lactide-co-caprolactone) nanofiber conduits for repair of nerve gap injury in a rat model. Methods: Ten-millimeter segments of sciatic nerve were resected in 44 Lewis rats. The gaps were either left unrepaired (n = 6), repaired with nerve autograft (n = 19), or repaired with conduit (n = 19). After 12 weeks, nerve conduction latency, compound muscle action potential amplitude, muscle force and muscle mass were measured. The numbers of axons and axon diameters both within the grafts and distally were determined. Results: After 12 weeks, gastrocnemius isometric tetanic force and muscle mass for the conduit group reached 85 and 82% of autograft values, respectively. Nerve conduction and compound muscle action potential were not significantly different between these two groups, although the latter approached significance. There was no recovery in the unrepaired group. Conclusion: Muscle recovery for the animals treated with this aligned nanofiber conduit approached that of autograft, suggesting the importance of internal conduit structure for nerve repair. © 2012 Future Medicine Ltd.

Fibrous polymer scaffolds and methods of manufacture are provided. The scaffolds can be formed of multiple layers and the extent and direction of alignment of each layer can be controlled. Efficient fabrication systems and methods for producing such scaffolds include apparatuses and processes are also provided. Kits including the fibrous polymer scaffolds and methods for implanting such scaffolds are also provided.

Nanonerve, Inc. | Entity website

ABOUT US We are a medical device company developing tissue engineered implant solutions for neurosurgery. Ourmission is to improve patient outcome by providing neurosurgeons with innovative solutions that encourage rapid neural tissue recovery and minimize complications ...

Kurpinski K.,Nanonerve, Inc. | Patel S.,Nanonerve, Inc.
Nanomedicine | Year: 2011

Aim: To create a synthetic nanofibrous dural substitute that overcomes the limitations of current devices by enhancing dural healing via biomimetic nanoscale architecture and supporting both onlaid and sutured implantation. Materials & methods: A custom electrospinning process was used to create a bilayer dural substitute having aligned nanofibers on one side and random nanofibers on the other. Nanoscale architecture was verified using microscopy and macroscale mechanical properties were investigated using tensile testing. Biological response to this device was investigated both in vitro and in a canine duraplasty model. Results & conclusion: Bilayer nanofiber alignment yields a graft having anisotropic mechanical properties with significantly higher strength and suturability than a commercially available collagen matrix. When implanted, the nanofibrous graft prevents leaks and brain tissue adhesions, and encourages dura mater regrowth, performing comparably to the collagen matrix. Both in vitro fibroblast orientation and in vivo dural healing are enhanced by the aligned nanofibers. © 2011 Future Medicine Ltd.

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