Biotechnology to enhance regeneration of significant lengths of peripheral nerve (PN) and subsequent functional recovery remains a critical need. Patients with uncorrectable nerve injuries face permanent loss of motor control and/or sensation. Although PNs are intrinsically capable of regeneration, they can only do so unaided across small gaps. Grafting of autologous nerve remains the best option, but donor morbidity and supply limitations remain problematic. Synthetic conduits have entered the market but have been ineffective for large gaps. This Bioengineering Partnership aims to combine the biological benefits of the inherent regeneration process through use of mimics of natural growth enhancers with the off-the-shelf convenience of a synthetic conduit with superior chemical and mechanical properties. Three laboratories at Rutgers University have established an interdisciplinary collaboration to jointly address major hurdles for a peripheral regeneration device for repair of large gaps. Dr. Melitta Schachner has identified several novel compounds that enhance not only the speed of PNR, but improve the quality of nerve regeneration by preferentially targeting regenerating motoneurons to muscle. Dr. David Shreiber has developed innovative methods to graft and pattern these enhancers to clinically relevant hydrogels used as conduit fillers, increasing the duration of activity and providing spatial guidance. Lastly, Dr. Joachim Kohn has combined novel co- polymer design with advanced manufacturing approaches to develop biodegradable polymer conduits with the flexibility necessary for large gaps that are additionally capable of eluting the bioactive compounds in a controlled fashion. The research team proposes to (i) develop a versatile platform of degradable conduits with tunable degradation and controlled release profiles;and optimize (ii) the spatial presentation of immobilized enhancers on a supporting scaffold within the conduits, (iii) the temporal presentation of soluble enhancers released from the conduits, and (iv) test the efficacy of the device in a large-gap animal model. By establishing a close research partnership, the applying laboratories will not only avoid the pitfall of creating components that are mutually exclusive or marginally compatible, but will realize an advanced time frame to develop the best possible combination of these three components to enhance the speed and quality of PN regeneration.
This Bioengineering Research Partnership will combine and translate three technologies invented at Rutgers toward development of a device for repairing large gaps in injured peripheral nerves. Neurobiology, biomateri- als and bioengineering researchers will partner in laboratory and preclinical studies to create a prototype of an off-the-shelf nerve regeneration conduit.
|Loers, Gabriele; Astafiev, Steven; Hapiak, Yuliya et al. (2017) The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. J Neurochem 142:392-406|
|Bhatnagar, Divya; Bushman, Jared S; Murthy, N Sanjeeva et al. (2017) Fibrin glue as a stabilization strategy in peripheral nerve repair when using porous nerve guidance conduits. J Mater Sci Mater Med 28:79|
|Goyal, Ritu; Macri, Lauren K; Kaplan, Hilton M et al. (2016) Nanoparticles and nanofibers for topical drug delivery. J Control Release 240:77-92|
|Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva et al. (2016) Design of barrier coatings on kink-resistant peripheral nerve conduits. J Tissue Eng 7:2041731416629471|
|Bhatnagar, Divya; Dube, Koustubh; Damodaran, Vinod B et al. (2016) Effects of Terminal Sterilization on PEG-Based Bioresorbable Polymers Used in Biomedical Applications. Macromol Mater Eng 301:1211-1224|
|Loers, Gabriele; Saini, Vedangana; Mishra, Bibhudatta et al. (2016) Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions. J Neurochem 136:48-62|
|Lowe, Christopher J; Reucroft, Ian M; Grota, Matthew C et al. (2016) Production of Highly Aligned Collagen Scaffolds by Freeze-drying of Self-assembled, Fibrillar Collagen Gels. ACS Biomater Sci Eng 2:643-651|
|Ezra, Mindy; Bushman, Jared; Shreiber, David et al. (2016) Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety. Tissue Eng Part A 22:818-26|
|Kaplan, Hilton M; Mishra, Prakhar; Kohn, Joachim (2015) The overwhelming use of rat models in nerve regeneration research may compromise designs of nerve guidance conduits for humans. J Mater Sci Mater Med 26:226|
|Bushman, J; Mishra, B; Ezra, M et al. (2014) Tegaserod mimics the neurostimulatory glycan polysialic acid and promotes nervous system repair. Neuropharmacology 79:456-66|
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