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In JoVE (1)
Other Publications (2)
Articles by Joseph R. Loverde in JoVE
JoVE Bioengineering
Axon Stretch Growth: The Mechanotransduction of Neuronal Growth
1Departments of Biomedical Engineering, New Jersey Institute of Technology, 2Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey
A unique tissue engineering method was developed to elongate numerous nerve fibers in culture by recapitulating axon stretch growth; a form of nervous system growth whereby nerves elongate in conjunction with growth of the enlarging body.
Other articles by Joseph R. Loverde on PubMed
Biomedical Engineering Strategies for Peripheral Nerve Repair: Surgical Applications, State of the Art, and Future Challenges
Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.
Live Imaging of Axon Stretch Growth in Embryonic and Adult Neurons
Strategies for nervous system repair arise from knowledge of growth mechanisms via a growth cone. The distinctive process of axon stretch growth is a robust, long-term growth that may reveal new pathways to accelerate nerve repair. Here, a live imaging bioreactor was engineered to closely explore cellular events initiated by applied tension. The stretch growth potential between adult and embryonic dorsal root ganglion (DRG) neurons was investigated, an important difference in nerve repair. Embryonic axons were capable of unidirectional stretch growth rates of 4?mm/d and reliably reached 4?cm in length within 2 weeks. Adult axons could only reach 2?mm/d and took over 3 weeks to reach 4?cm. Utilizing time-lapse imaging, we observed growth cone motility in coordination with stretch growth. Upon initiation of stretching, growth cones retracted. However, within 10?h of continuous stretching, growth cones extended at a rate of 0.2?mm/d opposite the direction of applied tension, contributing to overall axon elongation. We analyzed fast mitochondrial transport under increasing levels of strain to determine the effect of stretch on axonal transport. Transport began to diminish at 24% strain, and was almost completely absent at 39% strain. Surprisingly, axons recovered and were capable of subsequent stretch growth. When tension was completely released (?5% strain), stretch grown axons retracted at rates up to 6.1??m/sec and slowed as resting tension was restored. This ability to assess the process of axon stretch growth in real time will allow detailed study of how tension can be used to drive axonal growth and retraction.
