Abstract: Enhanced Nerve Regeneration By Minimizing Intraneural Scarring Using a Semi-Permeable Nanofiber Wrap (Plastic Surgery 2014)

Saturday, October 11, 2014: 10:40 AM

Karim A Sarhane, MD, MSc , Plastic Surgery, Johns Hopkins Medical Institutions, Baltimore, MD

Zuhaib Ibrahim, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Chris Cashman, MD/PhD candidate , Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD

Russel Martin, PhD candidate , Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD

Kellin Krick, PhD candidate , Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD

Sami H Tuffaha, MD , Plastic Surgery, Johns Hopkins Medical Institutions, Baltimore, MD

Justin M Broyles, MD , Plastic Surgery, Johns Hopkins Medical Institutions, Baltimore, MD

Baohan Pan, MD, PhD , Department of Neurology, Johns Hopkins University, Baltimore, MD

Nijaguna Prasad, PhD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Sepehr Tehrani, MD candidate , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Mohammed Alrakan, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Christopher Wallner, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Damon S Cooney, MD, PhD , Plastic and Reconstructive Surgery, Johns Hopkins Medical Institutions, Baltimore, MD

Ruifa Mi, MD, PhD , Department of Neurology, Johns Hopkins University, Baltimore, MD

Ahmet Höke, M.D., Ph.D. FRCPC , Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD

W. P. Andrew Lee, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Hai-Quan Mao, PhD , Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD

Gerald Brandacher, MD , Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD

Presentation PDF file

Introduction:

Despite great advances in microsurgery, functional outcomes following nerve repair remain suboptimal. Scar formation at the repair site is recognized as a major impediment to regenerating axons that need to cross the injury site. We examined the efficacy of a novel nanofiber nerve wrap in reducing scarring at the repair site to restore nerve continuity, enhance neuro-regeneration, and optimize functional recovery.

Methods:

Nerve wraps comprised of nonwoven electrospun poly (ε-caprolactone) nanofibers with pores smaller than 10 ľm and a thickness of 100 ľm were synthesized. They were wrapped around the nerve repair site in a sciatic transection/repair model in Thy-1 GFP rats. At 5 weeks, their neuro-protective effects and neuro-regenerative potential were assessed. In addition, at 16 weeks, functional recovery was evaluated.

Results:

At 5 weeks, the nanofiber wraps resulted in significantly decreased collagen deposition (Masson Trichrome) and inflammation/macrophage invasion (co-immunofluorescence staining) at the repair site. Moreover, the number of regenerating axons was significantly increased, and retrograde labeling revealed a trend towards a higher number of regenerated dorsal root ganglion neurons in the presence of nanofiber wraps. Mechanistically, these outcomes were correlated to an up-regulation of the anti-inflammatory cytokine (IL-10) and down-regulation of the pro-inflammatory cytokine (TNF-α). In addition, at 16 weeks, the nerve wrap group showed enhanced functional recovery as demonstrated by electromyography, neuromuscular junction re-innervation, and gastrocnemius muscle weight.

Conclusion:

Our results demonstrate favorable outcomes of a novel semi-permeable electrospun nanofiber nerve wrap in protecting the coaptation site and enhancing axonal regeneration through scar-free nerve repair resulting in optimizing functional recovery.

Effect Of a Semi-Permeable Nanofiber Wrap on Nerve Regeneration	*Evaluation at 5 weeks*				*Evaluation at 16 weeks*
	Regenerated myelinated axons (counts)	Collagen deposition (% area)	Macrophage infiltration (cells/mm²)	qRT-PCR (fold change)	EMG (% recovery)	NMJ (% reinnervation)	Gastroc. weight (% atrophy)
Group 1: Sciatic Transection and Repair	8,372 ą 1,691	7.4 ą 1.3	32.2 ą 2.4	Ref.	15.0 ą 4.7	3.1 ą 3.2	69.3 ą 6.0
Group 2: Sciatic Transection and Repair + Nerve Wrap	23,227 ą 4,527*	3.2 ą 1.3*	14.6 ą 1.8*	IL-10: +10 TNF-α:-5	23.2 ą 6.1	13.4 ą 4.7*	54.9 ą 6.9*
Mean ą standard deviation values are shown (n = 4-8). *p < 0.05 compared with control (Group 1).

25818 Enhanced Nerve Regeneration By Minimizing Intraneural Scarring Using a Semi-Permeable Nanofiber Wrap