Tissue-engineered constructs for peripheral nerve repair: current research concepts and future perspectives (original) (raw)
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Journal of The Royal Society Interface, 2012
Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative-hollow nerve guidance conduits (NGCs)-have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.
Daly et al 2011 A biomaterials approach to peripheral nerve repair
Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative-hollow nerve guidance conduits (NGCs)-have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic.
BIOMATERIALS FOR PERIPHERAL NERVE REGENERATION
Journal of Applied Science and Computations, 2018
Treating peripheral nerve injury is a major clinical challenge owing to the limited ability of the peripheral nerves to regenerate itself. Conventional treatment methods such as coaptation, autografting and xenografting possess inherent drawbacks such as reduced nerve stretching capacity, neuroma formation etc. To overcome these limitations, artificial nerve grafts employing natural or synthetic biomaterials are being developed. Axonal guidance structures and luminal fillers such as Schwann cells, stem cells, or nerve growth factors are also incorporated in the grafts to enhance their functionality. This paper reviews some of the biomaterials used in peripheral nerve regeneration, various modifications incorporated in them and their efficiency in aiding nerve repair.
Engineering an artificial nerve graft for the repair of severe nerve injuries
Medical & Biological Engineering & Computing, 2003
Nerve repair with tubes has a limit to regeneration depending upon the length of the gap. The characteristics of the guide, in terms of permeability, durability and adhesiveness, also influence regeneration. Considering the importance of the cellular component in regeneration, the development of artificial grafts, composed of a biocompatible nerve guide filled with a neurotropic matrix and seeded with Schwann cells (SCs), is an interesting option to enhance nerve regeneration and provide an alternative to the classical autologous nerve graft. We evaluated the ability of SCs transplanted into a nerve guide to improve regeneration after sciatic nerve resection, leaving a 6-mm gap, in the mouse. Syngeneic, isogeneic and autologous SCs were suspended in Matrigel and seeded in resorbable guides, and compared to acellular guides and to nerve autografts. The immunogenicity of the transplanted SCs clearly influenced the outcome. Transplants of autologous SCs resulted in only slightly lower levels of reinnervation than autografts, but higher recovery and number of regenerated axons than transplants of isologous and syngeneic SCs, and than acellular guides. Thus, by combined developments on nerve guides, extracellular matrix components and cell transplantation, an artificial graft has been designed that allows axonal regeneration across long gaps to levels comparable with an autograft.
Fundamentals and Current Strategies for Peripheral Nerve Repair and Regeneration
Advances in Experimental Medicine and Biology
A body of evidence indicates that peripheral nerves have an extraordinary yet limited capacity to regenerate after an injury. Peripheral nerve injuries have confounded professionals in this field, from neuroscientists to neurologists, plastic surgeons, and the scientific community. Despite all the efforts, full functional recovery is still seldom. The inadequate results attained with the "gold standard" autograft procedure still encourage a dynamic and energetic research around the world for establishing good performing tissue engineered alternative grafts. Resourcing to nerve guidance conduits, a variety of methods have been experimentally used to bridge peripheral nerve gaps of limited size, up to 30-40 mm in length, in humans. Herein, we aim to summarize the fundamentals related to peripheral nerve anatomy and overview the challenges and scientific evidences related to peripheral nerve injury and repair mechanisms. The most relevant reports dealing with the use of both synthetic and naturalbased biomaterials used in tissue engineering strategies when treatment of nerve injuries is envisioned are also discussed in depth, along with the state-of-the-art approaches in this field.
Frontiers in Bioengineering and Biotechnology
The use of autografted nerve in surgical repair of peripheral nerve injuries (PNI) is severely limited due to donor site morbidity and restricted tissue availability. As an alternative, synthetic nerve guidance channels (NGCs) are available on the market for surgical nerve repair, but they fail to promote nerve regeneration across larger critical gap nerve injuries. Therefore, such injuries remain unaddressed, result in poor healing outcomes and are a limiting factor in limb reconstruction and transplantation. On the other hand, a myriad of advanced biomaterial strategies to address critical nerve injuries are proposed in preclinical literature but only few of those have found their way into clinical practice. The design of synthetic nerve grafts should follow rational criteria and make use of a combination of bioinstructive cues to actively promote nerve regeneration. To identify the most promising NGC designs for translation into applicable products, thorough mode of action studie...
Tissue engineering is the science of tissue design to improve and repair tissue lesions. Peripheral nerves are normally prone to physical damage. Spontaneous repair of the peripheral nerve is usually not complete. Researchers in neural tissue engineering have developed channels that can help repair neural tissue, depending on the type of conformity and its ingredients. Functional recovery after peripheral nerve injury depends on the proper regeneration of axons in the direction of their primary target tissues. The use of transplant-based surgery is limited due to the lack of donors and the need to perform several operations. Tissue engineering with the design of nerve canals is one of the therapeutic approaches to replace damaged nerve tissue. For this purpose, this article examines the characteristics of the ideal channel for nerve repair to treat nerve lesions.
Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit
Frontiers in Bioengineering and Biotechnology
Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies.
Recent Approaches for Augmenting Peripheral Nerve Regeneration: Mini Review
MOJ Surgery
Injury to superficial or deeply seated nerve is commonly reported in human and animals causing crippling morbidity. The sciatic nerve is the most frequently involved nerve in such injuries. There could be several approaches for the repair of injured peripheral nerves. However, recent therapeutic approaches include the use of molecular, cellular and electrophysical methods. Mesenchymal stem cells are the most commonly used adult stem cells for the therapeutic purpose. Several studies have shown that stem cell transplantation may promote neural regeneration by enhanced growth factor secretion, extracellular matrix production and differentiation into Schwann cell, which are primarily responsible for the axonal regeneration. Scaffolds are used to maintain cell viability, support cell proliferation and permit intercellular communication. ECM proteins, and nerve growth factors can be incorporated into nerve conduits in order to improve the nerve regenerative ability. Among the electro physical methods use of 20Hz electrical stimulation, No thermal Laser Amnion Wrap and Thermal Laser Welding have shown promising results. The present review focuses on the application and outcome of important molecular, cellular and electro physical methods used for nerve regeneration.