Berkeley, CA, United States
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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.


Zhu Y.,University of California at Berkeley | Zhu Y.,University of California at San Francisco | Wang A.,University of California at Berkeley | Patel S.,Nanonerve, Inc. | And 6 more authors.
Tissue Engineering - Part C: Methods | Year: 2011

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. © 2011 Mary Ann Liebert, Inc.


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 Women's 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.


PubMed | Naval Medical Center Portsmouth, Uniformed Services University of the Health Sciences and Nanonerve, Inc.
Type: Journal Article | Journal: The Journal of surgical research | Year: 2016

Full-thickness soft tissue defects from congenital absence or traumatic loss are difficult to surgically manage. Healing requires cell migration, organization of an extracellular matrix, inflammation, and wound coverage. PLCL (70:30 lactide:caprolactone, Purac), poly(propylene glycol) nanofibrous scaffolds enhance cell infiltration invitro. This study compares strength and tissue ingrowth of aligned and unaligned nanofibrous scaffolds to absorbable and permanent meshes. We hypothesize that PLCL nanofibrous grafts will provide strength necessary for physiological function while serving as a scaffold to guide native tissue regeneration invivo.Abdominal wall defects were created in 126 rats followed by underlay implantation of Vicryl, Gore-Tex, aligned, or unaligned PLCL Nanofiber mesh. Specimens were harvested at 2, 6, and 12wk for strength testing and 2, 12, and 24wk for histopathologic evaluation. Specimens were graded for cellular infiltration, multinucleated giant cells (MNG), vascularity, and tissue organization. Mean scores were compared and analyzed with non-parametric testing.The PLCL grafts maintained structural integrity until at least 12wk and exhibited substantial tissue replacement at 24wk. At 12wk, only the aligned PLCL had persistent cellular infiltration of the graft, whereas both aligned and unaligned PLCL grafts showed the presence of MNG. The presence of MNGs decreased in the aligned PLCL graft by 24wk.The aligned PLCL nanofiber mesh offers early strength comparable to Gore-Tex but breaks down and is replaced with cellular ingrowth creating a favorable option in management of complex surgical wounds or native soft tissue defects.


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.


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.


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.


Fibrous polymer scaffolds having at least one layer of diametrically patterned fibers, as well as 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. Fabrication systems and methods for producing such scaffolds including apparatuses and processes are also provided.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.35M | Year: 2013

DESCRIPTION provided by applicant NanoNerve is developing a novel diametrically patterned nanofibrous dural substitute for rapid dura mater regeneration following neurosurgical procedures In the US alone neurosurgical procedures are performed annually that require patching of the dura mater to prevent leakage infection and neural damage Currently available dural substitutes include xenogenic collagen matrices and permanent synthetic devices Xenogeneic collagen matrices have significant disadvantages including low mechanical strength low suturability and high cost and disease transmission risks The permanent synthetic devices also suffer from major disadvantages including resistance to dura mater regeneration need for extensive suturing during implantation and higher leakage rates The overall goal of the project is FDA K clearance and commercialization of a highly versatile diametrically patterned nanofibrous dural substitute NanoNerve is utilizing its patent pending electrospinning technology to diametrically pattern nanofibers for rapidly regenerating dural tissue from the entire periphery of the defect toward the center NanoNerveandapos s synthetic bioresorbable nanofibrous dural substituteandapos s ultra thin profile and high mechanical strength will enable it to become the first synthetic dural substitute capable of sutured and suture free implantation This Phase II project will continue development of the diametrically patterned nanofibrous dural substitute by performing biocompatibility safety stability and long term in viv implantation studies Upon achievement of Phase II milestones NanoNerve will file an FDA IDE application for human clinical testing and eventually an FDA k for market clearance PUBLIC HEALTH RELEVANCE Over neurosurgical procedures are performed annually that require grafting of the dura mater to prevent fluid leakage infection and neural tissue damage Currently available dural substitutes have major limitations including incomplete dural repair low mechanical strength and high leakage rate complications This phase II study will enable development of a strong versatile and diametrically patterned nanofibrous dural substitute for rapid and effective dura mater regeneration


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 427.73K | Year: 2011

DESCRIPTION (provided by applicant): NanoNerve is developing a novel diametrically patterned nanofibrous dural substitute for rapid dura mater regeneration following neurosurgical procedures. In the US alone, 225,000 neurosurgical procedures are performedannually that require patching of the dura mater to prevent leakage, infection and neural damage. Currently available dural substitutes include xenogenic collagen matrices and permanent synthetic devices. Xenogenic collagen matrices have significant disadvantages including low mechanical strength, low suturability, high cost and disease transmission risks. The permanent synthetic devices also suffer from major disadvantages including resistance to dura mater regeneration, need for extensive suturing duringimplantation and higher leakage rates. The overall goal of the project is FDA 510(K) clearance and commercialization of a highly versatile diametrically patterned nanofibrous dural substitute. NanoNerve is utilizing its patent pending electrospinning technology to diametrically pattern nanofibers for rapidly regenerating dural tissue from the entire periphery of the defect toward the center. NanoNerve's synthetic bioresorbable nanofibrous dural substitute's ultra-thin profile and high mechanical strength will enable it to become the first synthetic dural substitute capable of sutured and suture-free implantation. This Phase I project will assess the biological performance of the diametrically patterned nanofibrous dural substitute and compare against two leading commercial products in an acute canine duraplasty model. Successful completion of Phase I milestones will enable biocompatibility, stability and long-term in vivo implantation studies in Phase II. Upon achievement of Phase II milestones, NanoNerve will file an FDA IDE application for human clinical testing. PUBLIC HEALTH RELEVANCE: Over 225,000 neurosurgical procedures are performed annually that require grafting of the dura mater to prevent fluid leakage, infection and neural tissue damage. Currently available dural substitutes have major limitations including incomplete dural repair, low mechanical strength and high leakage rate complications. This phase I study will enable development of a strong, versatile and diametrically patterned nanofibrous dural substitute for rapid and effective dura mater regeneration.

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