scholarly journals ‘EngNT’ — Engineering live neural tissue for nerve replacement

Author(s):  
James B. Phillips

Peripheral nerve injury can result in severe long-term disability and current clinical approaches for repairing large gaps rely on the nerve autograft. Engineered Neural Tissue (EngNT) has been developed to provide living aligned therapeutic cells in a stabilised collagen hydrogel, mimicking the key features of the autograft. This Perspective article will introduce the field and discuss the current stage of translation, highlighting the key opportunities for commercial and clinical development.

2011 ◽  
Vol 115 (5) ◽  
pp. 1084-1092 ◽  
Author(s):  
Maarten Swartjes ◽  
Aurora Morariu ◽  
Marieke Niesters ◽  
Michael Brines ◽  
Anthony Cerami ◽  
...  

Background Exogenous erythropoietin inhibits development of allodynia in experimental painful neuropathy because of its antiinflammatory and neuroprotective properties at spinal, supraspinal, and possibly peripheral sites. The authors assess the effect of a nonhematopoietic erythropoietin analog, ARA290, on tactile and cold allodynia in a model of neuropathic pain (spared nerve injury) in rats and mice lacking the β-common receptor (βcR mice), a component of the receptor complex mediating tissue protection. Methods Twenty-four hours after peripheral nerve injury, rats and mice were injected with ARA290 or vehicle (five 30-μg/kg intraperitoneal injections at 2-day intervals, followed by once/week, n = 8/group). In a separate group of eight rats, ARA290 treatment was restricted to five doses during the initial 2 weeks after surgery. Results In rats, irrespective of treatment paradigm, ARA290 produced effective, long-term (as long as 15 weeks) relief of tactile and cold allodynia (P < 0.001 vs. vehicle-treated animals). ARA290 was effective in wild-type mice, producing significant relief of allodynia. In contrast, in βcR mice no effect of ARA290 was observed. Conclusions ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.


Neuroreport ◽  
2001 ◽  
Vol 12 (16) ◽  
pp. 3439-3442 ◽  
Author(s):  
Richard B. Banati ◽  
Annachiara Cagnin ◽  
David J. Brooks ◽  
Roger N. Gunn ◽  
Ralph Myers ◽  
...  

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Hyoung Woo Kim ◽  
Chan Hee Won ◽  
Seog Bae Oh

Microglia activation following peripheral nerve injury has been shown to contribute to central sensitization of the spinal cord for the development of neuropathic pain. In a recent study, we reported that the amount of nerve damage does not necessarily correlate with chronic pain development. Here we compared the response of spinal microglia, using immunohistochemistry as a surrogate of microglial activation, in mice with two different types of crush injury of the sciatic nerve. We confirmed that incomplete crush of the sciatic nerve (partial crush injury, PCI) resulted in tactile hypersensitivity after the recovery of sensory function (15 days after surgery), whereas the hypersensitivity was not observed after the complete crush (full crush injury, FCI). We observed that immunoreactivity for Iba-1, a microglial marker, was greater in the ipsilateral dorsal horn of lumbar (L4) spinal cord of mice 2 days after FCI compared to PCI, positively correlating with the intensity of crush injury. Ipsilateral Iba-1 reactivity was comparable between injuries at 7 days with a significant increase compared to the contralateral side. By day 15 after injury, ipsilateral Iba-1 immunoreactivity was much reduced compared to day 7 and was not different between the groups. Our results suggest that the magnitude of the early microgliosis is dependent on injury severity, but does not necessarily correlate with the long-term development of chronic pain-like hypersensitivity after peripheral nerve injury.


1998 ◽  
Vol 102 (6) ◽  
pp. 2072-2081 ◽  
Author(s):  
Osamu Watanabe ◽  
Susan E. Mackinnon ◽  
Gregory Tarasidis ◽  
Daniel A. Hunter ◽  
Douglas J. Ball

2019 ◽  
Author(s):  
Justin C. Burrell ◽  
Kevin D. Browne ◽  
John L. Dutton ◽  
Suradip Das ◽  
Daniel P. Brown ◽  
...  

AbstractApproximately 20 million Americans currently experience residual deficits from traumatic peripheral nerve injury. Despite recent advancements in surgical technique, peripheral nerve repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with relatively slow rates of axonal regeneration. Development of novel surgical solutions requires valid preclinical models that adequately replicate the key challenges of clinical peripheral nerve injury. Our team has developed a porcine model using Yucatan minipigs that provides an opportunity to investigate peripheral nerve regeneration using different nerves tailored for a specific mechanism of interest, such as (1) nerve modality: motor, sensory, and mixed-modality; (2) injury length: short versus long gap; and (3) total regenerative distance: proximal versus distal injury. Here, we describe a comprehensive porcine model of two challenging clinically relevant procedures for repair of long segmental lesions (≥ 5 cm) – the deep peroneal nerve repaired using a sural nerve autograft and the common peroneal nerve repaired using a saphenous nerve autograft – each featuring ultra-long total regenerative distances (up to 20 cm and 27 cm, respectively) to reach distal targets. This paper includes a detailed characterization of the relevant anatomy, surgical approach/technique, functional/electrophysiological outcomes, and nerve morphometry for baseline and autograft repaired nerves. These porcine models of major peripheral nerve injury are suitable as preclinical, translatable models for evaluating the efficacy, safety, and tolerability of next-generation artificial nerve grafts prior to clinical deployment.


2010 ◽  
Vol 63 (11) ◽  
pp. 1893-1899 ◽  
Author(s):  
Jonas Pettersson ◽  
Daniel Kalbermatten ◽  
Aleksandra McGrath ◽  
Liudmila N. Novikova

2019 ◽  
Vol 12 (01) ◽  
pp. 27-31
Author(s):  
Benjamin Langridge ◽  
Michelle F. Griffin ◽  
M. A. Akhavani ◽  
Peter E. Butler

Abstract Introduction Peripheral nerve injuries in children are uncommon and can be challenging to diagnose. There is a paucity of data on long-term sensorimotor and functional outcomes following surgical repair. We present a 12-year retrospective analysis of pediatric peripheral nerve repair with long-term functional outcomes. Materials and Methods We performed a retrospective analysis of pediatric patients with peripheral nerve injury requiring surgical repair. Clinical records were analyzed for procedure type, time to surgery, mechanism of injury, postoperative recovery, and complications. Results A total of 108 patients were identified and 87 patients were included. Out of 87 patients, 83 (95.4%) had partial or complete sensorimotor recovery at final follow-up and 4 did not improve. Minor complications occurred in 10.3% of patients, all resolved with conservative management. Mechanisms of injury were predominantly lacerations with sharp objects or crush injuries. Age at time of injury was inversely correlated with sensorimotor recovery, and time to surgical repair was not. Conclusion Surgical repair with long-term hand therapy results in excellent functional outcomes following pediatric peripheral nerve injury. A low threshold for exploration and repair should be used in instances of diagnostic uncertainty. Timing of surgical repair is dependent on a patient’s clinical presentation; however, repair within 48 hours is sufficient for optimal sensorimotor recovery.


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