TitleThe design and fabrication of novel polyanhydride blend scaffolds for peripheral nerve repair
NameGriffin, Jeremy (author), Uhrich, Kathryn (chair), Shreiber, David (internal member), Lee, KiBum (internal member), Meiners, Sally (outside member), Stopek, Joshua (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionImplantable biodegradable nerve guidance conduits (NGCs) are promising alternatives to autograft nerve for tissue regeneration. The conduit scaffolds have the potential to align and support regenerating cells and prevent scar formation. Following laceration, natural peripheral nerve regeneration is an inefficient process involving obstructive scar formation and random axon re-growth. A synthetic nerve graft material must be able to: interact favorably with the cellular components of nerve tissue, be strong and pliable, and ideally biodegrade when regeneration is complete, leaving the biological structure intact. This research is directed towards engineering a biodegradable polymer-based NGC. Initial studies included in vitro bioassays and in vivo material evaluation using a novel α,α’-bis(o-carboxyphenoxy)-p-xylene-based polyanhydride blend NGC material. In vitro cytotoxicity studies with both immortal and primary cells demonstrated that the proposed polyanhydride blend is cytocompatible. Subcutaneous implantation for seven days in rats resulted in an initial fibrin matrix, minimal macrophage presence, and angiogenesis in the surrounding tissues. NGCs fabricated from the proposed polyanhydride blend material prove to serve as favorable biocompatible tissue engineering devices. Subsequent research was focused on developing porous bioactive scaffolds for nerve regeneration. An admixture of polylactide anhydride and a salicylic acid-based poly(anhydride-ester) was fabricated into conduits via a dip-coating technique. The addition of a plasticizer and porogen alleviates brittle mechanical properties and introduces porosity into the biomaterial. Under physiological conditions, the polymer conduit undergoes surface erosion and pH-dependent non-enzymatic hydrolytic bond cleavage. The polymer conduits degrade to release non-steroidal anti-inflammatory active therapeutics for several weeks. The NGCs were fully characterized in preparation for an in vivo study with the mouse femoral nerve model. Lastly, a hollow tissue engineering conduit may be augmented with an interior scaffold to most effectively mimic the native nerve microenvironment and facilitate nerve regeneration. Aligned poly(lactic-co-glycolic acid)/bioactive-polyanhydride fibrous substrates were fabricated through optimized electrospinning parameters. Neurons and glial cells demonstrated elongated and healthy proliferation in a direction parallel to orientated electrospun fibers with significantly longer outgrowth when compared to randomly orientated fibers. Aligned fiber mats have the potential to supplement the interior lumen of a degradable polymer NGC.
NoteIncludes bibliographical references
Noteby Jeremy Griffin
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.