Abstract
The regenerative capacity of the peripheral nervous system after an injury is limited, and a complete function is not recovered, mainly due to the loss of nerve tissue after the injury that causes a separation between the nerve ends and to the disorganized and intermingled growth of sensory and motor nerve fibers that cause erroneous reinnervations. Even though the development of biomaterials is a very promising field, today no significant results have been achieved. In this work, we study not only the characteristics that should have the support that will allow the growth of nerve fibers, but also the molecular profile necessary for a specific guidance. To do this, we carried out an exhaustive study of the molecular profile present during the regeneration of the sensory and motor fibers separately, as well as of the effect obtained by the administration and inhibition of different factors involved in the regeneration. In addition, we offer a complete design of the ideal characteristics of a biomaterial, which allows the growth of the sensory and motor neurons in a differentiated way, indicating (1) size and characteristics of the material; (2) necessity to act at the microlevel, on small groups of neurons; (3) combination of molecules and specific substrates; and (4) temporal profile of those molecules expression throughout the regeneration process. The importance of the design we offer is that it respects the complexity and characteristics of the regeneration process; it indicates the appropriate temporal conditions of molecular expression, in order to obtain a synergistic effect; it takes into account the importance of considering the process at the group of neuron level; and it gives an answer to the main limitations in the current studies.
Highlights
The peripheral nervous system (PNS) is responsible for connecting the periphery with the central nervous system, transmitting sensory signals, from the sensors to the brain and motor and from the brain to the muscles and glands
In this article, (i) we offer an understandable synthesis of the regeneration processes after a peripheral nerve injury (PNI) and the role that neurotrophic molecules play in those processes; (ii) we create a framework and rationale to be able to engineer therapeutic solutions based on biomaterials and molecules scientifically and non-empirically neurotrophic; and (iii) we propose biomimetic approaches for the development of advanced bio-hybrid devices to be used in severe PNI and in nerve–machine interfaces for amputee people
The above experimental data lead us to formulate the two biological principles that govern the regeneration of the peripheral nerves: (1) the separation of the fibers and their guidance toward their corresponding targets depend on the dynamics of the molecular gradients along the regeneration pathway, rather than on the concentration of the factors themselves; and (2) the molecules underlining these regenerative processes act at the microscopic level and not at the macroscopic one
Summary
The peripheral nervous system (PNS) is responsible for connecting the periphery with the central nervous system, transmitting sensory signals, from the sensors to the brain (afferent) and motor and from the brain to the muscles and glands (efferent). An essential feature of the PNS is the regenerative capacity it presents after suffering damage. Depending on the degree of damage, the number of damaged nerve structures, and the proximity to the nucleus, especially important for its role in the activation of the regenerative machinery (regeneration associated genes), regeneration will be more or less complete. The two main problems were (i) the distance or gap that is generated between the two ends of the damaged nerve and (ii) the intermingled growth of sensory and motor fibers that leads to erroneous reinnervation of the target tissues, sensors, and muscle fibers, respectively Livingstone Ltd., £ 12 10s, 1969; Sulaiman and Gordon, 2013)
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