Empty Conduit Research Articles

A Fluid Dynamic Development Like None Other

For more than 100 years, much uncertainty has surrounded fluid flow characteristics, both in open pipes and packed conduits. Not the least amongst this uncertainty has been the physics of the viscous boundary layer, in the former, and the so-called “wall-effect”, in the latter. Indeed, no fluid flow model has ever been able to reconcile both packed and empty conduits within the same theoretical framework, until now. In this paper, we describe the Quinn Fluid Flow Model (QFFM), which was first published in 2019 and represents the first model to capture, seamlessly, the physics of both empty and packed conduits, including all elements of wall-effects. This is not the only distinguishing feature of the model, which also includes, again, for the first time, a theoretical description of the so-called “constants” within the pressure flow relationship in closed conduits. Consequently, this model enables fluid dynamic validation over the entire fluid flow regime from creeping flow, at low Reynolds number values, to fully turbulent, at high Reynolds number values. This unique feature is possible because, on the one hand, in empty conduits, extremely large Reynolds number values are achievable at reasonable pressure drops but, very low Reynolds number values are not, due to the pressure drops being prohibitively low. In packed conduits, on the other hand, very low Reynolds number values are achievable at reasonable pressure drops but, large Reynolds number values are not, due to the pressure drops being prohibitively high. Accordingly, the QFFM enables simultaneous validation, at high Reynolds number values in the former and, at low Reynolds number values in the latter. This characteristic, therefore, to validate over the entire fluid flow regime using the same underlying physical and mathematical framework, sets this fluid flow model apart from all others. In addition to highlighting the many features of the QFFM in this paper, we will also demonstrate a comprehensive validation over ten orders of magnitude of the Reynolds number using published classical studies, as well as home grown experiments. To our knowledge, no extant fluid flow model comes even close to this comprehensive description of the fluid dynamics of fluid flow, not only in closed conduits, but also, by extrapolation, in other applications outside of this very narrow field of study.

"Peripheral Nerve Matrix hydrogel promotes recovery after nerve transection and repair."

Nerve transection is the most common form of peripheral nerve injury. Treatment of peripheral nerve injury has primarily focused on stabilization and mechanical cues to guide extension of the regenerating growth cone across the site of transection. Here we investigate the effects of a peripheral nerve matrix (PNM) hydrogel on recovery following nerve transection. We use rodent models to determine the effect of PNM on axon extension, electrophysiological nerve conduction, force generation and neuromuscular junction formation after nerve transection and repair. We complemented this work with in vivo and in vitro FACS and immunohistochemistry approaches to determine the effects of PN on critical cell populations early after repair. Extension of axons from the proximal stump and overall GFP+ axon volume within the regenerative bridge were increased in the presence of PNM compared with an empty conduit (p< 0.005) 21 days after repair. PNM increased electrophysiological conduction (CMAP amplitude) across the repair site (p<0.05) and neuromuscular junction formation (p=0.04) 56 days after repair. PNM produced a shift in macrophage phenotype in vitro and in vitro (p<0.05) and also promoted regeneration in a murine model used to characterize the early immune response to PNM (p<0.05). PNM, delivered by subepineural injection, promoted recovery following nerve transection with immediate repair, supporting a beneficial macrophage response, axon extension and downstream remodeling using a range of clinically relevant outcome measures.

Effects of Altering Magnesium Metal Surfaces on Degradation In Vitro and In Vivo during Peripheral Nerve Regeneration.

In vivo use of biodegradable magnesium (Mg) metal can be plagued by too rapid a degradation rate that removes metal support before physiological function is repaired. To advance the use of Mg biomedical implants, the degradation rate may need to be adjusted. We previously demonstrated that pure Mg filaments used in a nerve repair scaffold were compatible with regenerating peripheral nerve tissues, reduced inflammation, and improved axonal numbers across a short-but not long-gap in sciatic nerves in rats. To determine if the repair of longer gaps would be improved by a slower Mg degradation rate, we tested, in vitro and in vivo, the effects of Mg filament polishing followed by anodization using plasma electrolytic oxidation (PEO) with non-toxic electrolytes. Polishing removed oxidation products from the surface of as-received (unpolished) filaments, exposed more Mg on the surface, produced a smoother surface, slowed in vitro Mg degradation over four weeks after immersion in a physiological solution, and improved attachment of cultured epithelial cells. In vivo, treated Mg filaments were used to repair longer (15 mm) injury gaps in adult rat sciatic nerves after placement inside hollow poly (caprolactone) nerve conduits. The addition of single Mg or control titanium filaments was compared to empty conduits (negative control) and isografts (nerves from donor rats, positive control). After six weeks in vivo, live animal imaging with micro computed tomography (micro-CT) showed that Mg metal degradation rates were slowed by polishing vs. as-received Mg, but not by anodization, which introduced greater variability. After 14 weeks in vivo, functional return was seen only with isograft controls. However, within Mg filament groups, the amount of axonal growth across the injury site was improved with slower Mg degradation rates. Thus, anodization slowed degradation in vitro but not in vivo, and degradation rates do affect nerve regeneration.

The Proposed Unshell Directive – The Luxembourg and Netherlands Approach

In this article, the author presents the features of the Proposed Unshell Directive (COM(2021) 565 final) in the context of the existing legislative framework of Luxembourg and the Netherlands. In particular, the article focuses on the legislative measures taken by Luxembourg and the Netherlands in recent years to reduce the use of empty conduits and the perception of the Proposed Unshell Directive in those two countries.

Muography as a new complementary tool in monitoring volcanic hazard: implications for early warning systems

Muography uses muons naturally produced in the interactions between cosmic rays and atmosphere for imaging and characterization of density differences and time-sequential changes in solid (e.g. rocks) and liquid (e.g. melts ± dissolved gases) materials in scales from tens of metres to up to a few kilometres. In addition to being useful in discovering the secrets of the pyramids, ore prospecting and surveillance of nuclear sites, muography successfully images the internal structure of volcanoes. Several field campaigns have demonstrated that muography can image density changes relating to magma ascent and descent, magma flow rate, magma degassing, the shape of the magma body, an empty conduit diameter, hydrothermal activity and major fault lines. In addition, muography is applied for long-term volcano monitoring in a few selected volcanoes around the world. We propose using muography in volcano monitoring in conjunction with other existing techniques for predicting volcanic hazards. This approach can provide an early indication of a possible future eruption and potentially the first estimate of its scale by producing direct evidence of magma ascent through its conduit in real time. Knowing these issues as early as possible buy critically important time for those responsible for the local alarm and evacuation protocols.

Nerve-specific extracellular matrix hydrogel promotes functional regeneration following nerve gap injury

Nerve transection requires surgical intervention to restore function. The standard of care involves coaptation when a tension-free repair is achievable, or interposition of a graft or conduit when a gap remains. Despite advances, nerve gap injury is associated with unsatisfactory recovery. This study investigates the use of a decellularized, porcine nerve-derived hydrogel filler (peripheral nerve matrix, PNM) for conduits in an 8 mm rat sciatic nerve gap model. The decellularized tissue maintained multiple nerve-specific matrix components and nerve growth factors. This decellularized tissue was used to formulate hydrogels, which were deployed into conduits for nerve gap repair. Nerve recovery was assessed up to 24 weeks post injury by gait analysis, electrophysiology, and axon counting. Deployment of PNM within conduits was shown to improve electrophysiologic response and axon counts compared with those of empty conduit controls. These results indicate that PNM has potential benefits when used as a filler for conduits in nerve gap injuries.

Rapidly formed stable and aligned dense collagen gels seeded with Schwann cells support peripheral nerve regeneration

Objective. Gel aspiration-ejection (GAE) has recently been developed for the rapid production of dense, anisotropic collagen gel scaffolds with adjustable collagen fibrillar densities. In this study, a GAE system was applied to produce aligned Schwann cells within a type-1 collagen matrix to generate GAE-engineered neural tissues (GAE-EngNT) for potential nerve tissue engineering applications. Approach. The stability and mechanical properties of the constructs were investigated along with the viability, morphology and distribution of Schwann cells. Having established the methodology to construct stable robust Schwann cell-loaded engineered neural tissues using GAE (GAE-EngNTs), the potential of these constructs in supporting and guiding neuronal regeneration, was assessed both in vitro and in vivo. Main results. Dynamic mechanical analysis strain and frequency sweeps revealed that the GAE-EngNT produced via cannula gauge number 16 G (∼1.2 mm diameter) exhibited similar linear viscoelastic behaviors to rat sciatic nerves. The viability and alignment of seeded Schwann cells in GAE-EngNT were maintained over time post GAE, supporting and guiding neuronal growth in vitro with an optimal cell density of 2.0 × 106 cells ml−1. An in vivo test of the GAE-EngNTs implanted within silicone conduits to bridge a 10 mm gap in rat sciatic nerves for 4 weeks revealed that the constructs significantly promoted axonal regeneration and vascularization across the gap, as compared with the empty conduits although less effective regeneration compared with the autograft groups. Significance. Therefore, this is a promising approach for generating anisotropic and robust engineered tissue which can be used with Schwann cells for peripheral nerve repair.

Quinn’s Law of Fluid Dynamics: Supplement #3 A Unique Solution to the Navier-Stokes Equation for Fluid Flow in Closed Conduits

The recent publication of Quinn’s Law of Fluid Dynamics brings into focus longstanding contradictions regarding permeability in closed conduits that have littered the fluid dynamics landscape for more than 150 years. In this paper, we will use this new level of understanding to explain these contradictions, in layman’s terms, and resolve them, by introducing for the first time, as far as we know, a unique solution to the Navier-Stokes equation for fluid flow in closed conduits, which is understandable by knowledgeable physicists, engineers, chromatographers and aerospace enthusiasts alike, but who may not necessarily be versed in the abstract jargon of a graduate in advanced mathematics. In addition, we will apply our unique solution to chosen illustrative worked examples, as well as those of third parties from the published literature. In so doing, we will demonstrate the utility of our solution, not only, to packed conduits containing particles having solid skeletons, but also, to empty conduits, which in the context of this new understanding of fluid dynamics in closed conduits, represents a special case of a packed conduit in which the particles are fully porous, i.e., they are made entirely of free space.

Quinn’s Law of Fluid Dynamics: Supplement #1 Nikuradze’s Inflection Profile Revisited

This paper is directed at the important contribution to fluid dynamics made by Johan Nikuradze. His seminal paper published in 1933 represents the gold standard of empty conduit permeability, for the flow of water through roughened pipes, even to this very day. We revisit in some detail the “inflection profile” in Nikuradze’s plot, which appears in the curve for his roughened data found in Figure 9 in that publication. In so doing, we show that the data points at low Reynolds number values, and particularly those surrounding the value of 3.4 approximately on the x-axis of his plot, do not represent the reported experimental results found in his tables of data. Furthermore, we also demonstrate that this discrepancy in his original paper is very problematic because it forms the basis for many subsequent scholarly works. As a result, this inflection profile has become erroneously embedded in conventional folklore concerning fluid flow in closed conduits and has enjoyed widespread acceptance as being a legitimate feature of fluid dynamics dogma. With the advent recently of Quinn’s Law, a novel approach to the understanding of fluid flow in closed conduits, we are able to articulate in a manner not heretofore possible, the significance of this discrepancy which is far too important to ignore.

Combining Magma Flow and Deformation Modeling to Explain Observed Changes in Tilt

The understanding of magma ascent dynamics is essential in forecasting the scale, style and timing of volcanic eruptions. The monitoring of near-field deformation is widely used to gain insight into these dynamics, and has been linked to stress changes in the upper conduit. The ascent of magma through the conduit exerts shear stress on the conduit wall, pulling up the surrounding edifice, whilst overpressure in the upper conduit pushes the surrounding edifice outwards. H\sout{owever, h}ow much shear stress and pressure is produced during magma ascent, and the relative contribution of each to the deformation, \sout{is yet to be fully understood and quantified}\textcolor{blue}{has until now only been explored conceptually}. By combining flow and deformation modelling using COMSOL Multiphysics, we \sout{are} for the first time \sout{able to}\textcolor{blue}{present a quantitative model that links magma ascent to deformation. We} quantify how both shear stress and pressure vary spatially within a conduit, and show that shear stress generally dominates observed changes in tilt close to the conduit during activity at Tungurahua volcano, Ecuador, between 2013 and 2014. However, the relative contribution of pressure is not insignificant, and \sout{the full stress tensor comprising} both pressure and shear stress must be considered when interpreting deformation data. We demonstrate that significant changes in tilt \sout{can occur as magma refills an empty conduit, or} can be driven by changes in the driving pressure gradient or volatile content of the magma. The relative contribution of shear stress and pressure to the tilt varies considerably depending on these parameters. Our work provides insight into the range of elastic moduli that should be considered when modelling edifice-scale rock masses, and we show that even where the edifice is modelled as weak, shear stress \textcolor{blue}{generally} dominates the near field deformation over pressurisation of the conduit.

Nerve Conduit Enhancement with Vomeronasal Organ Improves Rat Sciatic Functional Index in a Segmental Nerve Defect Model

Segmental nerve loss presents a challenge to the reconstructive surgeon. Collagen nerve conduits are one strategy for reconstruction of segmental defects, but no conduit-based reconstructive strategy has been as successful as autograft reconstruction. We hypothesized that collagen nerve conduits used to bridge segmental sciatic nerve defects may be enhanced by grafting with vomeronasal organ (VNO), owing to this tissue’s capacity for regeneration. Fourteen rats underwent resection of a 1.0 cm segment of sciatic nerve. Seven rats underwent reconstruction of the defect using a commercially available collagen nerve conduit. Seven rats underwent reconstruction using conduit filled with fresh VNO allograft. An additional seven rats underwent transection and direct epineural repair. Fourteen weeks postoperatively, all animals underwent calculation of sciatic functional index (SFI) via walking track analysis. After sacrifice, tissues were processed for histomorphometric analysis, including axon quantification and axon density. All reconstructed nerves were in continuity at sacrifice. At 14 weeks, the mean SFI was significantly higher in the vomeronasal organ-enhanced (VNOE) group and epineural repair (ER) group than the conduit-only (CO) group. `SFI was equivalent between VNOE and ER groups. Axon density was greater in the VNOE and ER groups than the CO group. Axon density was equivalent between VNOE and ER groups. In conclusion, this rat sciatic nerve segmental defect model achieved greater functional recovery and axon density using collagen nerve conduits filled with a pluripotent neuroepithelium relative to reconstruction with an empty conduit. These results suggest a promising strategy for repair of segmental peripheral nerve defects.

RGD-Modified Nanofibers Enhance Outcomes in Rats after Sciatic Nerve Injury.

Nerve injuries requiring surgery are a significant problem without good clinical alternatives to the autograft. Tissue engineering strategies are critically needed to provide an alternative. In this study, we utilized aligned nanofibers that were click-modified with the bioactive peptide RGD for rat sciatic nerve repair. Empty conduits or conduits filled with either non-functionalized aligned nanofibers or RGD-functionalized aligned nanofibers were used to repair a 13 mm gap in the rat sciatic nerve of animals for six weeks. The aligned nanofibers encouraged cell infiltration and nerve repair as shown by histological analysis. RGD-functionalized nanofibers reduced muscle atrophy. During the six weeks of recovery, the animals were subjected to motor and sensory tests. Sensory recovery was improved in the RGD-functionalized nanofiber group by week 4, while other groups needed six weeks to show improvement after injury. Thus, the use of functionalized nanofibers provides cues that aid in in vivo nerve repair and should be considered as a future repair strategy.

Quinn’s Law of Fluid Dynamics Pressure-driven Fluid Flow Through Closed Conduits

In this paper we develop from first principles a unique law pertaining to the flow of fluids through closed conduits. This law, which we call “Quinn’s Law”, may be described as follows: When fluids are forced to flow through closed conduits under the driving force of a pressure gradient, there is a linear relationship between the fluid-drag normalized dimensionless pressure gradient, PQ, and the normalized dimensionless fluid current, CQ. The relationship is expressed mathematically as: PQ=k1 +k2CQ. This linear relationship remains the same whether the conduit is filled with or devoid of solid obstacles. The law differentiates, however, between a packed and an empty conduit by virtue of the tortuosity of the fluid path, which is seamlessly accommodated within the normalization framework of the law itself. When movement of the fluid is very close to being at rest, i.e., very slow, this relationship has the unique minimum constant value of k1, and as the fluid acceleration increases, it varies with a slope of k2 as a function of normalized fluid current. Quinn’s Law is validated herein by applying it to the data from published classical studies of measured permeability in both packed and empty conduits, as well as to the data generated by home grown experiments performed in the author’s own laboratory.

Electrophysiological assessment of a peptide amphiphile nanofiber nerve graft for facial nerve repair.

Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with (1) an intact nerve, (2) following resection of a nerve segment, and following resection and immediate repair with either a (3) autograft (using the resected nerve segment), (4) neurograft, or (5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes whereas nerve compound action potentials (nCAPs) and electromygraphic responses were recorded. After 8weeks, the proximal buccal branch was surgically reexposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft, and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and transmission electron microscopy confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair.

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Statement of SignificanceDecellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy of decellularized nerve allograft for nerve regeneration, with limited success. Xenogeneic decellularized tissue matrices or hydrogels have been widely used for surgical applications owing to their ease of harvesting and low immunogenicity. Moreover, decellularized tissue matrix hydrogels show good biocompatibility and are highly tunable. In this study, we prepared a porcine decellularized nerve matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our results demonstrate that pDNM-G can support Schwann cell proliferation and peripheral nerve regeneration by means of residual primary extracellular matrix components and nano-fibrous structure features.

Constructing conductive conduit with conductive fibrous infilling for peripheral nerve regeneration

Nerve conduits are essential for guiding the regeneration of injured peripheral nerves, and empty conduits usually cannot perform satisfactorily due to problems with cell migration and nutrient transportation. Taking the electrophysiological features of nervous tissues into consideration, in this study, a conductive conduit filled with parallel-aligned conductive fibers was constructed, and its potential for enhancing peripheral nerve regeneration was evaluated in vivo. The conductive fibers were prepared via depositing a polypyrrole (PPY) shell onto electrospun parallel-aligned poly(lactide-co-glycolide) (PLGA) fibers. The conductive conduit was prepared from PLGA/PPY emulsion via dip-coating on a mandrel. Both materials were non-cytotoxic to PC12 cells and were able to promote cell proliferation and differentiation. Moreover, the aligned fibers provided strong orientation guidance for nerve fibers. Sciatic nerve defects were created in Sprague-Dawley rats, and empty or fiber-filled conduits were sutured into the defects. Meanwhile, the control groups received PLGA conduits or autografts. Twelve weeks post-operation, the fiber-filled conductive conduit showed much better nerve regeneration outcomes than both the PLGA conduit and the empty conductive conduit and showed comparable results to the autograft in terms of electrophysiological properties, sciatic function indices, and regenerated myelinated nerve fibers as well as axon diameter and myelin thickness. It is possible that the oriented conductive fibers in the conductive conduit provide a favorable micro-environment for nerve growth due to their capacity to transmit self-originated electrical stimulation between cells. The results of animal testing confirmed the feasibility of using combined conductive conduits for guiding nerve regeneration.

A new technique for probing the internal structure of volcanoes using cosmic-ray muons

Among the considerable number of studies that can be carried out using muons, we pay specific attention to the radiography of volcanoes based on the same principle of the X-ray radiography of human body. Thanks to their high penetration capability, cosmic-ray muons can be used to reconstruct the density distribution of the interior of huge structures by measuring the attenuation induced by the material on the muon flux. In particular, the quantitative understanding of the inner structure of volcanoes is a key-point to forecast the dangerous stages of activity and mitigate volcanic hazards. The instrumental approach is currently based on the detection of muons crossing hodoscopes made up of scintillator planes. Unfortunately, these detectors are affected by a strong background comprised by accidental coincidence of vertical shower particles, horizontal high-energy electrons and upward going particles. We propose an alternative technique based on the detection of the Cherenkov light produced by muons. This can be achieved with an imaging atmospheric Cherenkov telescope composed of a high reflectivity optical system that focus the Cherenkov light onto a multi-pixel focal camera with fast read-out electronics. The Cherenkov light emitted by a muon is imaged on the camera as an annular pattern which contains information to reconstruct the direction of the incident muon. We have estimated that using the Cherenkov imaging technique for muon radiography of volcanoes gives the advantage of a negligible background and improved spatial resolution, compared to the majority of the particle detectors. We present results of simulations based on a telescope with a positioning resolution of 13.5 m which corresponds to an acceptance of 9 cm2 sr. The telescope is located 1500 m far from a toy-model volcano, namely, a cone with a base diameter of 500 m and a height of 240 m. We test the feasibility of the proposed method by estimating the minimum number of observation nights needed to resolve inner empty conduits of different diameter.

Short and long gap peripheral nerve repair with magnesium metal filaments

A current clinical challenge is to replace autografts for repair of injury gaps in peripheral nerves, which can occur due to trauma or surgical interruption. Biodegradable metallic magnesium filaments, placed inside hollow nerve conduits, could support nerve repair by providing contact guidance support for axonal regeneration. This was tested by repairing sciatic nerves of adult rats with single magnesium filaments placed inside poly(caprolactone) nerve conduits. Controls were empty conduits, conduits containing titanium filaments and/or isografts from donor rats. With a nerve gap of 6 mm and 6 weeks post-repair, magnesium filaments had partially resorbed. Regenerating cells had attached to the filaments and axons were observed in distal stumps in all animals. Axon parameters were improved with magnesium compared to conduits alone or conduits with single titanium filaments. With a longer gap of 15 mm and 16 weeks post-repair, functional parameters were improved with isografts, but not with magnesium filaments or empty conduits. Magnesium filaments were completely resorbed and no evidence of scarring was seen. While axon outgrowth was not improved with the longer gap, histological measures of the tissues were improved with magnesium compared to empty conduits. Therefore, the use of magnesium filaments is promising because they are biocompatible and improve aspects of nerve regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3148-3158, 2017.

Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration.

Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.

Hyaluronic acid/carboxymethyl cellulose directly applied to transected nerve decreases axonal outgrowth

Neuroma management is an unresolved problem. Biomaterials to limit unwanted axonal growth could be a tool to manage neuroma. Hyaluronic acid/carboxymethyl cellulose (HA/CMC) is an antiadhesive, biodegradable material that is nontoxic to nerve. The purpose of this study was to evaluate the efficacy of this biomaterial to limit axonal growth. Rats received a sciatic nerve transection and repair with a short conduit (5 mm) containing HA/CMC, fibrin, or nothing (empty conduit). In another study, nerve was transected and either left undisturbed or wrapped with HA/CMC around the proximal and distal ends. In a final study, nerve was transected and repaired with an HA/CMC wrap. Four weeks following the procedures, nerves were harvested and assessed using histomorphometry to measure axonal regeneration. Axonal regeneration following transection was significantly inhibited by direct axonal contact with HA/CMC, whether within a conduit or wrapped around the transected proximal nerve end. Axonal regeneration following epineurial repair was not affected by HA/CMC wrapped around nerve, demonstrating axonal growth inhibition due to direct contact of regenerating axons with HA/CMC. These studies demonstrate the efficacy of HA/CMC to limit axonal outgrowth by contact with regenerating axons. HA/CMC barriers may prove to be a tool to prevent neuroma formation by inhibiting axonal growth. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 568-574, 2017.