Description:
OBJECTIVE: The objective of this effort is to develop a new innovative technology that may include the use of novel materials, nanotopology, cellular/tissue-based strategies or biologics, to accelerate peripheral nerve regeneration and functional recovery in defects greater than 3 cm. DESCRIPTION: Segmental nerve defects have limited potential for spontaneous recovery and are often associated with devastating functional deficiencies. It is known that 5-6% of all military injuries involve major injury to a peripheral nerve. Before World War II (WW II) nerve injuries were repaired as simple reapproximation and suturing procedures often conducted under tension. They were often further complicated by surrounding tissue damage and infection. Poor outcomes from these procedures were discovered to be the result of failed axonal regeneration at the site of repair. Here we recognize the need for medical interventions to address large gap (>3 cm) peripheral nerve injuries. While tension-free autografting remains the gold standard in the field it may not be appropriate in cases where extensive injury prohibits the use of autologus tissue (i.e. sural nerve harvest) from the wounded warrior. Early research in the field also demonstrated success with tissue based ensheathment approaches. In recent times conduits and scaffolds of allogenic or synthetic matrices that provide guidance for axonal regeneration now show much promise. As the therapeutic field continues to advance, it is likely nanotopology, cellular, mechanical, biologic or pharmacological components may also be incorporated to facilitate the repair of larger peripheral nerve defects (gaps>3cm). Technologies proposed under this topic should address the current limitations of available technologies or propose new technologies intended to promote the efficient and reproducible repair of peripheral nerve defects as defined by functional improvement and provide an alternative to autograft harvest PHASE I: Conceptualize and design an innovative solution which will promote the repair and regeneration of large gap peripheral nerve defects (>3 cm) ultimately targeting functional improvement of the affected tissues. Such technologies may include biomaterials, nanotopology, cellular, tissue or biological components meant to facilitate controlled axonal outgrowth or promote ensheathment. It is likely that the most successful constructs may incorporate two or more of the described components. The required Phase I deliverables will include: 1) a research design for the proposed technology that is intended to provide some preliminary in vitro supporting evidence for addressing nerve defects (to be executed at Phase I), and 2) A preliminary prototype or composition of matter description with supporting rationale. Other supportive data from in vivo proof-of-concept studies demonstrating tissue or organ reinnervation which lead to functional improvement may also be provided during this 6-month Phase I, $100K (max) effort. PHASE II: The researcher shall design, develop, test, finalize and validate the practical implementation of the prototype technology that implements the Phase I methodology to promote peripheral nerve defect repair over this 2-year, $1.0M (max) effort. The researcher shall also describe in detail the transition plan for the Phase III effort. PHASE III: Plans on the commercialization/technology transition and regulatory pathway should be executed here and lead to FDA clearance/approval. They include: 1) identifying a relevant patient population for clinical testing to evaluate safety and efficacy, and 2) GMP manufacturing sufficient materials for evaluation. The small business should also provide a strategy to secure additional funding from non-SBIR government sources and /or the private sector to support these efforts. Military application: The desired therapy will allow military practitioners to apply the therapy. Commercial application: Healthcare professionals world-wide could utilize this product as a therapy meant to improve the standard of care presently available to patients suffering from large gap peripheral nerve defects. REFERENCES: 1."Immediate Care of the Wounded."Clifford C. Cloonan. Copyright 2007 The Brookside Associates, Ltd. All Rights Reserved http://www.operationalmedicine.org/TextbookFiles/Cloonan/Disability.pdf 2."Acute nerve injury."Medscape Reference., Sep 23, 2011. http://emedicine.medscape.com/article/249621-overview# 3."Peripheral nerve reconstruction using freezethawed muscle grafts: a comparison with group fascicular nerve grafts in a large animal model."J.R. Coll. Surg. Edinb., October 1998; Vol 43; p295-302. http://www.rcsed.ac.uk/journal/vol43_5/4350024.htm 4."Processed allografts and type I collagen conduits for repair of peripheral nerve gaps."Mucsle & Nerve. June 2009: Vol 39, Issue 6; p787-799. http://onlinelibrary.wiley.com/doi/10.1002/mus.21220/pdf
