A Novel Bioengineered Conduit Reduces Neuroma Formation After Targeted Muscle Reinnervation
Erica Lee, MS, Bruce Enzmann, BS, Thomas Harris, MBChB, Alison Wong, MD, Sai Pinni, BS, Nicholas von Guionneau, MBBS, Ruchita Kothari, BS, Michael Lan, BME, Chenhu Qiu, BS, Anson Zhou, BME, Alyssa Lee, BS, Jaimie Shores, MD, Alban Latremoliere, MD, Lintao Qu, PhD, Ahmet Hoke, MD PhD, Hai-Quan Mao, PhD, Sami Tuffaha, MD.
Johns Hopkins School of Medicine, Baltimore, MD, USA.
Purpose: Targeted muscle reinnervation (TMR) outcomes may be limited by axonal escape and consequential neuroma formation at the often size-mismatched coaptation. To overcome this concern, we developed a funnel-shaped conduit to mechanically guide regenerating axons across the coaptation. Given the limited capacity of the distal nerve to accept axons regenerating from the larger proximal nerve, we incorporated chondroitin sulfate proteoglycans (CSPGs) within the conduits to inhibit a portion of the regenerating axons.
Methods: A conduit device composed of nonwoven poly-ε-caprolactone, was developed by electrospinning. Within the conduit, CSPGs incorporated into a nanofiber hydrogel form an interpenetrating network. Using a TMR rodent hindlimb model, we tested the effects of this device with and without CSPGs on neuroma formation.
Results: The significant size mismatch at the coaptation site between the sciatic nerve and tibial branch to the lateral gastrocnemius muscle resulted in neuroma formation in the TMR group, while the use of the conduit resulted in tapered reinnervation of the sciatic nerve, demonstrating the effectiveness of this device in mechanically guiding axonal growth. Pain scores elicited by mechanical stimulation at the coaptation site were significantly lower in the CSPG-conduit group as compared to the Neuroma, TMR, and Empty Conduit groups (p<0.0001), suggesting successful prevention of neuroma formation.
Conclusions: This novel bioengineered conduit presents a biologically compatible, readily translatable means by which we could optimize TMR postoperative outcomes. 
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