FIGURE 3 - uploaded by Laura Rodríguez Doblado
Content may be subject to copyright.
| Bundles of axons in the nervous system. (A) Peripheral nerve anatomy. (B) Myelinated (left) and unmyelinated (right) nerve fibers in the peripheral nervous system. (C) Spinal cord tracts divided in sensory or ascending tracts (blue) and motor or descending tract (red) to illustrate the complexity of the tract organization in the spinal cord. (D) Dopaminergic pathways as an example of the large number of pathways inside the brain. Dopaminergic pathways are the bundles of neuron projections in the brain that synthesize and release the neurotransmitter dopamine. Alterations in these pathways may be involved in multiple diseases and disorders such as Parkinson's disease, addiction, or attention deficit hyperactivity disorder.
Source publication
The therapy of neural nerve injuries that involve the disruption of axonal pathways or axonal tracts has taken a new dimension with the development of tissue engineering techniques. When peripheral nerve injury (PNI), spinal cord injury (SCI), traumatic brain injury (TBI), or neurodegenerative disease occur, the intricate architecture undergoes alt...
Contexts in source publication
Context 1
... cell bodies of sensory neurons are located in adjacent structures to the spinal cord [dorsal root ganglion (DRG)] or in cranial ganglia, while the cell bodies of motor neurons are within the CNS (spinal cord or brainstem) ( Noback et al., 1968). Each nerve of the PNS consists of three essential tissue elements: axons, SC (and myelin sheaths), and connective tissue (endoneurium, perineurium, and epineurium) ( Figure 3A). In the PNS, there are also ganglia, formed by cell bodies and satellite cells associated with the peripheral nerves. ...
Context 2
... all nerve fibers over 3 µm in diameter are myelinated, and those under <3 µm are unmyelinated. Only one SC encapsulates a myelinated nerve fiber, but a group of unmyelinated fibers might share the same SC ( Figure 3B) (Grinsell and Keating, 2014). Bundle axons of the CNS are located in the white matter. ...
Context 3
... of the motor pathways form groups referred to as descending tracts, carrying information from the brain to the peripheral effectors (muscles and glands). So, the spinal cord consists of a large number of ascending and descending tracts, each located in particular parts of the dorsal, lateral, or ventral column of the white matter ( Figure 3C) (Mai and Paxinos, 2012). In the brain, there are many axonal pathways. ...
Context 4
... example is the axonal pathways between the substantia nigra pars compacta (SNpc) and the striatum, which is altered in Parkinson's disease. SNpc neurons send long-projecting axons to the striatum, and in Parkinson's disease, there is a selective loss of the dopaminergic neurons, so this neurodegeneration deprives the striatum of crucial dopaminergic inputs and causes ineffective feedback of motor pathway (Davie, 2008) (Figure 3D). ...
Similar publications
Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve in...
Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of A...
Peripheral nerve injury often occurs in young adults and is characterized by complex regeneration mechanisms, poor prognosis, and slow recovery, which not only creates psychological obstacles for the patients but also causes a significant burden on society, making it a fundamental problem in clinical medicine. Various steps are needed to promote re...
Citations
... Subsequently, cell death induced by necrosis or apoptosis occurs, leading to tissue loss. Therefore, there has been great interest in proposing innovative alternatives to restore nerve tissue [7][8][9]. The main challenge of tissue engineering is the functional repair of tissue injuries caused by wounds, diseases, infections, and ischemia by creating a suitable scaffold biomaterial that mimics natural tissue [10][11][12]. ...
... Cell-based therapies have shown great promise by targeting damaged axonal pathways. Still, the strategies proposed are not designed to restore longdistance axons; novel strategies enhance axons' intrinsic ability to regenerate and create a permissive environment for axonal outgrowth [8,62,63]. Transplantable "scaffolds" have recently been used to facilitate axon regeneration. Although this is a promising strategy, the results of in vitro tests show that the number and length of the axons that grow along the scaffolds have been limited [64][65][66][67]. ...
The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications.
... For what concerns nerve tissue engineering, some common scaffold formats and materials include fibers, conduits, membranes, and aligned scaffolds 126 , However, neural cells grow and develop optimally when provided with spherical or cylindrical structures, likely due to their resemblance to natural neural elements like nerves, the spinal cord, or brain tracts 127 Altogether, these properties can tune a scaffold to support neurite outgrowth and differentiation of human neural stem cells 130,131 . ...
Recent advances in nanotechnology design and fabrication have shaped the landscape for the development of ideal cell interfaces based on biomaterials. A holistic evaluation of the requirements for a cell...
... Recent studies have investigated strategies to optimize the degradation kinetics of biomaterials to match the regenerative timeline of brain tissue and prevent adverse reactions such as glial scarring. 123,124 In addition, the mechanical properties of biomaterials play a crucial role in their design. Recent literature has emphasized the need to tailor the stiffness, elasticity, and viscoelastic properties of biomaterials to mimic the mechanical properties of native brain tissue, providing appropriate mechanical support and minimizing tissue damage. ...
Numerous modalities exist through which the central nervous system (CNS) may sustain injury or impairment, encompassing traumatic incidents, stroke occurrences, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Presently available pharmacological and therapeutic interventions are incapable of restoring or regenerating damaged CNS tissue, leading to substantial unmet clinical needs among patients with CNS ailments or injuries. To address and facilitate the recovery of the impaired CNS, cell‐based repair strategies encompass multiple mechanisms, such as neuronal replacement, therapeutic factor secretion, and the promotion of host brain plasticity. Despite the progression of cell‐based CNS reparation as a therapeutic strategy throughout the years, substantial barriers have impeded its widespread implementation in clinical settings. The integration of cell technologies with advancements in regenerative medicine utilizing biomaterials and tissue engineering has recently facilitated the surmounting of several of these impediments. This comprehensive review presents an overview of distinct CNS conditions necessitating cell reparation, in addition to exploring potential biomaterial methodologies that enhance the efficacy of treating brain injuries.
... The future of polymers in the treatment of diseases of the central nervous system is extremely interesting and interdisciplinary, but also challenging and still not fully understood. The central nervous system is the most important system in the body, so it is important that proposed treatments using polymer scaffolds are safe and clinically tested [103][104][105]. ...
Biodegradable polymers are materials that, thanks to their remarkable properties, are widely understood to be suitable for use in scientific fields such as tissue engineering and materials engineering. Due to the alarming increase in the number of diagnosed diseases and conditions, polymers are of great interest in biomedical applications especially. The use of biodegradable polymers in biomedicine is constantly expanding. The application of new techniques or the improvement of existing ones makes it possible to produce materials with desired properties, such as mechanical strength, controlled degradation time and rate and antibacterial and antimicrobial properties. In addition, these materials can take virtually unlimited shapes as a result of appropriate design. This is additionally desirable when it is necessary to develop new structures that support or restore the proper functioning of systems in the body.
... [1][2][3][4] To address these limitations, researchers have turned to original approaches that synergistically integrate concepts of regenerative medicine with biomaterial-based neural tissue engineering. [5,6] One of the fundamental design criteria for effective clinical translation emphasizes the use of biomaterials that recapitulate key physicochemical features of the intended target tissue to recreate a biomimetic microenvironment that ultimately enhances cell survival, guides differentiation, and promotes functional integration within the host tissue. Among the material properties deemed fundamental to achieve neuroregenerative abilities (e.g., biocompatibility, native tissue-like mechanical properties, and suitable degradation rate), [5,7] recent findings have highlighted the pivotal role of electroconductivity in guiding several developmental processes associated with cell proliferation and synaptic plasticity. ...
... [5,6] One of the fundamental design criteria for effective clinical translation emphasizes the use of biomaterials that recapitulate key physicochemical features of the intended target tissue to recreate a biomimetic microenvironment that ultimately enhances cell survival, guides differentiation, and promotes functional integration within the host tissue. Among the material properties deemed fundamental to achieve neuroregenerative abilities (e.g., biocompatibility, native tissue-like mechanical properties, and suitable degradation rate), [5,7] recent findings have highlighted the pivotal role of electroconductivity in guiding several developmental processes associated with cell proliferation and synaptic plasticity. [8][9][10] Based on this evidence, the use of electroconductive hydrogels has emerged as an effective approach to recapitulate the physicochemical and electrical microenvironment of neural tissues. ...
... The rationale behind this novel strategy is that collagen has already shown great promise as a therapeutic solution for central nervous system injuries and degeneration. [5,33,40] When used in its hydrogel form, collagen provides unique physicochemical and biological cues that support cellular adhesion, growth and proliferation. It is also a biopolymer approved by the FDA for clinical testing in neural tissue engineering and several collagen-based products are already commercially available. ...
Neuronal disorders are characterized by the loss of functional neurons and disrupted neuroanatomical connectivity, severely impacting the quality of life of patients. This study investigates a novel electroconductive nanocomposite consisting of glycine‐derived carbon nanodots (GlyCNDs) incorporated into a collagen matrix and validates its beneficial physicochemical and electro‐active cueing to relevant cells. To this end, this work employs mouse induced pluripotent stem cell (iPSC)‐derived neural progenitor (NP) spheroids. The findings reveal that the nanocomposite markedly augmented neuronal differentiation in NP spheroids and stimulate neuritogenesis. In addition, this work demonstrates that the biomaterial‐driven enhancements of the cellular response ultimately contribute to the development of highly integrated and functional neural networks. Lastly, acute dizocilpine (MK‐801) treatment provides new evidence for a direct interaction between collagen‐bound GlyCNDs and postsynaptic N‐methyl‐D‐aspartate (NMDA) receptors, thereby suggesting a potential mechanism underlying the observed cellular events. In summary, the findings establish a foundation for the development of a new nanocomposite resulting from the integration of carbon nanomaterials within a clinically approved hydrogel, toward an effective biomaterial‐based strategy for addressing neuronal disorders by restoring damaged/lost neurons and supporting the reestablishment of neuroanatomical connectivity.
... 100The potential of cell adhesion molecules extends beyond neuralelectrode interfaces in neuromodulation and neuroprosthetic systems, as previously mentioned, showcasing their versatility in various applications. Their versatility for modification extends beyond neural-electrode interfaces in neuromodulation and neuroprosthetic systems to encompass neural tissue engineering applications, including the utilization in nerve guidance conduits or drug delivery particles.2,101,102 ...
To provide a long‐term solution for increasing the biocompatibility of neuroprosthetics, approaches to reduce the side effects of invasive neuro‐implantable devices are still in need of improvement. Physical, chemical, and bioactive design aspects of the biomaterials are proven to be important for providing proper cell‐to‐cell, cell‐to‐material interactions. Particularly, modification of implant surfaces with bioactive cues, especially cell adhesion molecules (CAMs) that capitalize on native neural adhesion mechanisms, are promising candidates in favor of providing efficient interfaces. Within this concept, this study utilized specific CAMs, namely N‐Cadherin (Neural cadherin, N‐Cad) and neural cell adhesion molecule (NCAM), to enhance neuron‐electrode contact by mimicking the cell‐to‐ECM interactions for improving the survival of cells and promoting neurite outgrowth. For this purpose, representative gold electrode surfaces were modified with N‐Cadherin, NCAM, and the mixture (1:1) of these molecules. Modifications were characterized, and the effect of surface modification on both differentiated and undifferentiated neuroblastoma SH‐SY5Y cell lines were compared. The findings demonstrated the successful modification of these molecules which subsequently exhibited biocompatible properties as evidenced by the cell viability results. In cell culture experiments, the CAMs displayed promising results in promoting neurite outgrowth compared to conventional poly‐l‐lysine coated surfaces, especially NCAM and N‐Cad/NCAM modified surfaces clearly showed significant improvement. Overall, this optimized approach is expected to provide an insight into the action mechanisms of cells against the local environment and advance processes for the fabrication of alternative neural interfaces.
... They can be made from natural polymers to mimic native tissue extracellular matrix or synthetic polymers with linked agonists to improve neural tissue growth. In addition, modified bioscaffolds can secrete molecules to promote regeneration or be loaded with transplant cell populations for replacing damaged tissue (Doblado et al., 2021;Boni et al., 2018;Führmann et al., 2017). ...
Effective repair of spinal cord injury sites remains a major clinical challenge. One promising strategy is the implantation of multifunctional bioscaffolds to enhance nerve fiber growth, guide regenerating tissue, and modulate scarring/inflammation processes. Given their multifunctional nature, such implants require testing in models which replicate the complex neuropathological responses of spinal injury sites. This is often achieved using live, adult animal models of spinal injury. However, these have substantial drawbacks for developmental testing, including the requirement for large numbers of animals, costly infrastructure, high levels of expertise, and complex ethical processes. As an alternative, we show that organotypic spinal cord slices can be derived from the E14 chick embryo and cultured with high viability for at least 24 days, with major neural cell types detected. A transecting injury could be reproducibly introduced into the slices and characteristic neuropathological responses similar to those in adult spinal cord injury observed at the lesion margin. This included aligned astrocyte morphologies and upregulation of glial fibrillary acidic protein in astrocytes, microglial infiltration into the injury cavity, and limited nerve fiber outgrowth. Bioimplantation of a clinical grade scaffold biomaterial was able to modulate these responses, disrupting the astrocyte barrier, enhancing nerve fiber growth, and supporting immune cell invasion. Chick embryos are inexpensive and simple, requiring facile methods to generate the neurotrauma model. Our data show the chick embryo spinal cord slice system could be a replacement spinal injury model for laboratories developing new tissue engineering solutions. Plain language summary Spinal cord injury can be highly debilitating for patients and carers. Repair of the spinal cord is therefore a major clinical goal but is challenging owing to the complex pathology of the injury site. Researchers need to mimic this complexity in the laboratory to test new therapies in realistic environments. Traditionally, researchers use live, adult animal models to achieve this, which are highly traumatic, variable, and costly. Here, we show an alternative system based on slices of spinal cord tissue from chick embryos that could partially replace live adult animal testing. We show slices can be grown in a dish and reproducibly injured, with complex pathology replicated. Further, we modified cell responses in the injury through interface with a novel implant, potentially improving repair. The model is cost-effective, simple, and associated with less animal suffering than live adult animal experiments.
... Its strategies are being designed to promote new meniscus tissue in the inner white-white zone of the meniscus. Tissue engineering consists of three general components: scaffolds for cell support and transplantation, cells that can create a functional matrix, and bioactive factors that support and regulate cellular activity [7]. There are many commercialized cell-seeded scaffolds or pure scaffolds, but they are unfavorable for arthroscopic surgery. ...
This study aimed to develop poly (vinyl alcohol) grafted glycidyl methacrylate/cellulose nanofiber (PVA-g-GMA/CNF) injectable hydrogels for meniscus tissue engineering. PVA-g-GMA is an interesting polymer for preparing cross-linking injectable hydrogels with UV radiation, but it has poor mechanical properties and low cell proliferation. In this study, CNF as a reinforcing agent was selected to improve mechanical properties and cell proliferation in PVA-g-GMA injectable hydro-gels. The effect of CNF concentration on hydrogel properties was investigated. Both PVA-g-GMA and PVA-g-GMA hydrogels incorporating 0.3, 0.5, and 0.7% (w/v) CNF can be formed by UV curing at a wavelength of 365 nm, 6 mW/cm2 for 10 min. All hydrogels showed substantial microporosity with interconnected tunnels, and a pore size diameter range of 3–68 µm. In addition, all hydrogels also showed high physicochemical properties, a gel fraction of 81–82%, porosity of 83–94%, water content of 73–87%, and water swelling of 272–652%. The water content and swelling of hydrogels were increased when CNF concentration increased. It is worth noting that the reduction of porosity in the hydrogels occurred with increasing CNF concentration. With increasing CNF concentration from 0.3% to 0.7% (w/v), the compressive strength and compressive modulus of the hydrogels significantly increased from 23 kPa to 127 kPa and 27 kPa to 130 kPa, respectively. All of the hydrogels were seeded with human cartilage stem/progenitor cells (CSPCs) and cultured for 14 days. PVA-g-GMA hydrogels incorporating 0.5% and 0.7% (w/v) CNF demonstrated a higher cell proliferation rate than PVA-g-GMA and PVA-g-GMA hydrogels incorporating 0.3% (w/v) CNF, as confirmed by MTT assay. At optimum formulation, 10%PVA-g-GMA/0.7%CNF injectable hydrogel met tissue engineering requirements, which showed excellent properties and significantly promoted cell proliferation, and has a great potential for meniscus tissue engineering application.
... The variation between polymers and among different products of the same polymer is a potential limitation to translating natural polymers to commercial use because reproducibility is a critical factor in developing an optimal treatment. [15,[39][40][41][42][43]. ...
... Meanwhile, the body will have systemic and localized reactions to the implanted material. Following the standard pattern of wound healing after a nerve is damaged, the foreign object implanted in the injured area will interact with peripheral immune cells, fibroblasts, progenitor cells, and the neural and glial cells that form the body's nervous system [15,63,64]. The interactions between these cells and different biomaterials will determine if the entire construct is both biocompatible and capable of promoting functional nerve recovery. ...
... While there have been many studies on the effects of polymers, incorporating nanomaterials and cross-linking changes the material's characterization and the behavior of the cells they interact with [56]. In all, the goal of these modifications remains the same, to develop a safe and functional treatment for neural injuries [15]. ...
Neural injuries affect millions globally, significantly impacting their quality of life. The inability of these injuries to heal, limited ability to regenerate, and the lack of available treatments make regenerative medicine and tissue engineering a promising field of research for developing methods for nerve repair. This review evaluates the use of natural and synthetic polymers, and the fabrication methods applied that influence a cell’s behavior. Methods include cross-linking hydrogels, incorporation of nanoparticles, and 3D printing with and without live cells. The endogenous cells within the injured area and any exogenous cells seeded on the polymer construct play a vital role in regulating healthy neural activity. This review evaluates the body’s local and systemic reactions to the implanted materials. Although numerous variables are involved, many of these materials and methods have exhibited the potential to provide a biomaterial environment that promotes biocompatibility and the regeneration of a physical and functional nerve. Future studies may evaluate advanced methods for modifying material properties and characterizing the tissue–biomaterial interface for clinical applications.
... 144 To address this, a common approach is utilizing nerve guidance conduits (NGCs), which are devices that guide axonal growth, that lost the capacity to establish synaptic connections due to injury or degeneration. 145 Ye et al. propose the use of DLP-printed multichannel NGCs made from GelMA to aid regenerate peripheral nerves. 146 In brief, the fabricated NGCs were able to support the long-term survival, proliferation, and migration of PC-12 cells and induce neuronal differentiation from neural crest stem cells in vitro. ...
Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ replacements in hopes of restoring normal tissue function and structure. Generating the engineered organs with an infrastructure that is similar to that of the real organs can be beneficial to simulate the functional organs that work inside our bodies. Photopolymerization-based 3D bioprinting, or photocuring, has emerged as a promising method in engineering biomimetic tissues due to its simplicity, non-invasive, and spatially controllable approach. In this review, we investigated types of 3D printers, mainstream materials, photoinitiators, phototoxicity, and selected tissue engineering applications of 3D photopolymerization bioprinting.
