Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety

Ezra, Mindy; Bushman, Jared; Shreiber, David I.; Schachner, Melitta; Kohn, Joachim

doi:10.1089/ten.tea.2015.0354

Cited by 40 publications

(38 citation statements)

References 40 publications

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“…Despite these observations of modulated neurite growth by natural ECM hydrogel fillers, a comparison revealed that they were still outperformed by the “gold standard” autograft . Furthermore, a more recent study also indicated that the presence of natural ECM bulk hydrogel can expedite the infiltration of non‐neuronal cells into the conduit space, promoting fibrotic tissue formation and leading to impaired neural regeneration …”

Section: Isotropic Hydrogel Fillersmentioning

confidence: 99%

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

Wieringa

Pinho

Micera

et al. 2018

Adv Healthcare Materials

119

116

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Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration.

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Section: Isotropic Hydrogel Fillersmentioning

confidence: 99%

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

Wieringa

Pinho

Micera

et al. 2018

Adv Healthcare Materials

119

116

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“…Braided TyrPC NGTs also offer a very high degree of kink-resistance, allowing for over 120° of flexing without luminal occlusion [9]. Earlier small animal studies have demonstrated that TyrPC NGTs significantly enhance regeneration and functional recovery, and exhibit excellent mechanical strength, suturability, and flexibility [9][10][11][12].…”

Section: Discussionmentioning

confidence: 99%

“…More recently, braiding of polymer fibers has been introduced to generate porous NGTs with mechanical properties and flexibility suitable for nerve repair [7][8][9]. In this study, a braided NGT was fabricated using two polymers chosen from a library of tyrosine-derived polycarbonates (TyrPCs), which have previously been shown to facilitate nerve regeneration in rodent models and demonstrated improved functional recovery in small gap injuries [10][11][12]. While braiding may improve mechanical strength and increase kink-resistance, macropore structures may form allowing for tissue infiltration into the conduit that can hinder nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-Derived Polycarbonate Nerve Guidance Tubes Elicit Pro-Regenerative Extracellular Matrix Deposition When Used to Bridge Segmental Nerve Defects in Swine

Burrell

Bhatnagar

Brown

et al. 2020

Preprint

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Promising biomaterials for facilitating regeneration should be tested in appropriate large animal models that better recapitulate human inflammatory and regenerative responses than rodent models. Previous studies have shown tyrosine-derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of tissue engineering applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for the design of nerve guidance tubes (NGTs). NGTs made of different TyrPCs have been used in segmental nerve defect models in small animals. The current study is an extension of this work and evaluates the effects of NGTs made using two different TyrPC compositions in a porcine model of peripheral nerve injury and repair. We first evaluated a nondegradable TyrPC formulation in a 1 cm segmental nerve defect model in pigs, demonstrating proof-of-concept of chronic regenerative efficacy up to 6 months, at which time nerve/muscle electrophysiology and nerve morphometry were similar to those attained by an autograft repair control. Next, we characterized the acute regenerative response to a degradable TyrPC formulation using the same 1 cm segmental defect model. After 2 weeks in vivo, this TyrPC NGT was found to promote the deposition by host cells of pro-regenerative extracellular matrix (ECM) constituents (in particular collagen I, collagen III, collagen IV, laminin and fibronectin) at levels exceeding those deposited inside commercially available collagen-based NGTs. This corresponded with dense and rapid infiltration of host Schwann cells and axons into the lumen of the NGT and axonal crossing of the lesion into the distal nerve segment. These findings confirmed results reported previously in a mouse model and reveal that TyrPC NGTs were well tolerated in swine and facilitated host axon regeneration and Schwann cell infiltration in the acute phase across segmental defects -likely by eliciting a favorable neurotrophic ECM milieu. This regenerative response ultimately can contribute to functional recovery.

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“…Some research studies have reported that NGCs filled with inner filler in lumen can serve as guidance channel to enhance axonal regeneration compared to hollow NGCs . However, another researcher has mentioned that the inner filler may only be beneficial when it is impermeable to infiltrate fibrotic tissue . Thus, we designed hollow form of NGC for guiding infiltration of host nerve tissue migration for nerve regeneration along with micropattern and permeability for the inner layer of NGC.…”

Section: Discussionmentioning

confidence: 99%

“…[32] However, another researcher has mentioned that the inner filler may only be beneficial when it is impermeable to infiltrate fibrotic tissue. [33] Thus, we designed hollow form of NGC for guiding infiltration of host nerve tissue migration for nerve regeneration along with micropattern and permeability for the inner layer of NGC.…”

Section: Discussionmentioning

confidence: 99%

Biodegradable Nerve Guidance Conduit with Microporous and Micropatterned Poly(lactic‐co‐glycolic acid)‐Accelerated Sciatic Nerve Regeneration

Kim

Lee

Jeon

et al. 2018

Macromolecular Bioscience

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An innovative technique combining capillary force lithography and phase separation method in one step is applied to fabricate artificial nerve guidance conduit (NGC) for peripheral nerve regeneration. Biodegradable porous, patterned NGC (PP‐NGC) using poly(lactic‐co‐glycolic acid) is fabricated. It has micro‐grooves and microporosity on the inner surface to promote axonal outgrowth and to enhance permeability for nutrient exchange. In this study, it is confirmed that the inner surface of micro‐grooves can modulate neurite orientation and length of mouse neural stem cell compared to porous flat NGC (PF‐NGC) in vitro. Coating with 3,4‐dihydroxy‐l‐phenylalanine (DOPA) facilitates the hydrophilic inner surface of PF‐ and PP‐NGCs via bioinspired catechol chemistry. For in vivo study, PF‐NGC and PP‐NGC coated with or without DOPA are implanted in the 10 mm sciatic nerve defect margins between proximal and distal nerves in rats. Especially, PP‐NGC coated with DOPA shows higher sciatic function index score, onset‐to‐peak amplitude, and muscle fiber diameter compared to other groups. The proposed hybrid‐structured NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.

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Porous and Nonporous Nerve Conduits: The Effects of a Hydrogel Luminal Filler With and Without a Neurite-Promoting Moiety

Cited by 40 publications

References 40 publications

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

Tyrosine-Derived Polycarbonate Nerve Guidance Tubes Elicit Pro-Regenerative Extracellular Matrix Deposition When Used to Bridge Segmental Nerve Defects in Swine

Biodegradable Nerve Guidance Conduit with Microporous and Micropatterned Poly(lactic‐co‐glycolic acid)‐Accelerated Sciatic Nerve Regeneration

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