Effect of Dynamic Deformational Loading on the Transport of Dextran Molecules Into Agarose Gels

Author(s):  
Nadeen O. Chahine ◽  
Eric G. Lima ◽  
Clark T. Hung ◽  
Gerard A. Ateshian

The poor intrinsic healing capacity of articular cartilage has led to a number of attempts to engineer a replacement tissue [1]. One of these approaches, termed functional tissue engineering, suggests that the application of mechanical preconditioning, mimicking the in vivo loading environment, may enhance the development of material properties in these constructs [2,3]. Using this approach, our previous studies have demonstrated that dynamic loading (DL) increases the mechanical properties of chondrocyte-seeded agarose hydrogels relative to free swelling (FS) controls [4–6]. One mechanism by which the increase in mechanical properties occurs is hypothesized to be due to enhanced transport of nutrients and/or growth factors under dynamic loading [7]. The goal of the current study is to determine the effect of dynamic loading on the transport of neutral dextran molecules into agarose gels. Dextran, a neutral and generally inert solute commonly used in diffusion and transport studies, is used in its fluorophore-conjugated form thus making it possible to track the solute and quantify its content inside a hydrogel. We hypothesize that the uptake of dextran molecules into the agarose gels will be significantly enhanced under the influence of physiological dynamic deformation loading. Two varying molecular weights of dextran, 3 kDa and 70 kDa, were chosen in this study to ascertain a wide range of transport behaviors, and to interpret the experimental results in the context of a recently developed mixture theory model for the transport of neutral solutes in a neutrally charged gel, such as agarose [8].

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1027
Author(s):  
Vincenzo De Leo ◽  
Francesco Milano ◽  
Angela Agostiano ◽  
Lucia Catucci

Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore allow the low chemical versatility typical of lipids to be overcome. Moreover, depending on their structure, polymers can be used to create a simple covering on the liposome surface or to intercalate in the phospholipid bilayer to give rise to real hybrid structures. This review illustrates the main strategies implemented in the field of polymer/liposome assembly for drug delivery, with a look at the most recent publications without neglecting basic concepts for a simple and complete understanding by the reader.


Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 519
Author(s):  
Vitalii Bezgin ◽  
Agata Dudek ◽  
Adam Gnatowski

This paper proposes and presents the chemical modification of linear hydroxyethers (LHE) with different molecular weights (380, 640, and 1830 g/mol) with the addition of three types of rubbers (polysulfide rubber (PSR), polychloroprene rubber (PCR), and styrene-butadiene rubber (SBR)). The main purpose of choosing this type of modification and the materials used was the possibility to use it in industrial settings. The modification process was conducted for a very wide range of modifier additions (rubber) per 100 g LHE. The materials obtained in the study were subjected to strength tests in order to determine the effect of the modification on functional properties. Mechanical properties of the modified materials were improved after the application of the modifier (rubber) to polyhydroxyether (up to certain modifier content). The most favorable changes in the tested materials were registered in the modification of LHE-1830 with PSR. In the case of LHE-380 and LHE-640 modified in cyclohexanol (CH) and chloroform (CF) solutions, an increase in the values of the tested properties was also obtained, but to a lesser extent than for LHE-1830. The largest changes were registered for LHE-1830 with PSR in CH solution: from 12.1 to 15.3 MPa for compressive strength tests, from 0.8 to 1.5 MPa for tensile testing, from 0.8 to 14.7 MPa for shear strength, and from 1% to 6.5% for the maximum elongation. The analysis of the available literature showed that the modification proposed by the authors has not yet been presented in any previous scientific paper.


2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Brendon M. Baker ◽  
Nandan L. Nerurkar ◽  
Jason A. Burdick ◽  
Dawn M. Elliott ◽  
Robert L. Mauck

Aligned nanofibrous scaffolds hold tremendous potential for the engineering of dense connective tissues. These biomimetic micropatterns direct organized cell-mediated matrix deposition and can be tuned to possess nonlinear and anisotropic mechanical properties. For these scaffolds to function in vivo, however, they must either recapitulate the full dynamic mechanical range of the native tissue upon implantation or must foster cell infiltration and matrix deposition so as to enable construct maturation to meet these criteria. In our recent studies, we noted that cell infiltration into dense aligned structures is limited but could be expedited via the inclusion of a distinct rapidly eroding sacrificial component. In the present study, we sought to further the fabrication of dynamic nanofibrous constructs by combining multiple-fiber populations, each with distinct mechanical characteristics, into a single composite nanofibrous scaffold. Toward this goal, we developed a novel method for the generation of aligned electrospun composites containing rapidly eroding (PEO), moderately degradable (PLGA and PCL/PLGA), and slowly degrading (PCL) fiber populations. We evaluated the mechanical properties of these composites upon formation and with degradation in a physiologic environment. Furthermore, we employed a hyperelastic constrained-mixture model to capture the nonlinear and time-dependent properties of these scaffolds when formed as single-fiber populations or in multipolymer composites. After validating this model, we demonstrated that by carefully selecting fiber populations with differing mechanical properties and altering the relative fraction of each, a wide range of mechanical properties (and degradation characteristics) can be achieved. This advance allows for the rational design of nanofibrous scaffolds to match native tissue properties and will significantly enhance our ability to fabricate replacements for load-bearing tissues of the musculoskeletal system.


Author(s):  
Maoen Pan ◽  
Chaoqian Zhao ◽  
Zeya Xu ◽  
Yuanyuan Yang ◽  
Tianhong Teng ◽  
...  

Long-term placement of non-degradable silicone rubber pancreatic duct stents in the body is likely to cause inflammation and injury. Therefore, it is necessary to develop degradable and biocompatible stents to replace silicone rubber tubes as pancreatic duct stents. The purpose of our research was to verify the feasibility and biological safety of extrusion-based 3D printed radiopaque chitosan (CS) ducts for pancreaticojejunostomy. Chitosan-barium sulfate (CS-Ba) ducts with different molecular weights (low-, medium-, and high-molecular weight CS-Ba: LCS-Ba, MCS-Ba, and HCS-Ba, respectively) were soaked in vitro in simulated pancreatic juice (SPJ) (pH 8.0) with or without pancreatin for 16 weeks. Changes in their weight, water absorption rate and mechanical properties were tested regularly. The biocompatibility, degradation and radiopaque performance were verified by in vivo and in vitro experiments. The results showed that CS-Ba ducts prepared by this method had regular compact structures and good molding effects. In addition, the lower the molecular weight of the CS-Ba ducts was, the faster the degradation rate was. Extrusion-based 3D-printed CS-Ba ducts have mechanical properties that match those of soft tissue, good biocompatibility and radioopacity. In vitro studies have also shown that CS-Ba ducts can promote the growth of fibroblasts. These stents have great potential for use in pancreatic duct stent applications in the future.


1978 ◽  
Vol 100 (4) ◽  
pp. 194-201 ◽  
Author(s):  
J. C. Ziegert ◽  
J. L. Lewis

In order to measure in-vivo bone accelerations, it is necessary to know the mechanical response of the soft tissue covering areas of bony prominence when a load is applied through a rigid contactor. Two methods are presented for determining this response in vivo. The first method is for quasi-static loading and the second method is for dynamic loading at approximately 2000 Hz. Results are presented for various subjects and contactor geometries.


2005 ◽  
Vol 127 (1) ◽  
pp. 181-185 ◽  
Author(s):  
Paul S. Robinson ◽  
Tung-Fu Huang ◽  
Elan Kazam ◽  
Renato V. Iozzo ◽  
David E. Birk ◽  
...  

Evaluations of tendon mechanical behavior based on biochemical and structural arrangement have implications for designing tendon specific treatment modalities or replacement strategies. In addition to the well studied type I collagen, other important constituents of tendon are the small proteoglycans (PGs). PGs have been shown to vary in concentration within differently loaded areas of tendon, implicating them in specific tendon function. This study measured the mechanical properties of multiple tendon tissues from normal mice and from mice with knock-outs of the PGs decorin or biglycan. Tail tendon fascicles, patellar tendons (PT), and flexor digitorum longus tendons (FDL), three tissues representing different in vivo loading environments, were characterized from the three groups of mice. It was hypothesized that the absence of decorin or biglycan would have individual effects on each type of tendon tissue. Surprisingly, no change in mechanical properties was observed for the tail tendon fascicles due to the PG knockouts. The loss of decorin affected the PT, causing an increase in modulus and stress relaxation, but had little effect on the FDL. Conversely, the loss of biglycan did not significantly affect the PT, but caused a reduction in both the maximum stress and modulus of the FDL. These results give mechanical support to previous biochemical data that tendons likely are uniquely tailored to their specific location and function. Variances such as those presented here need to be further characterized and taken into account when designing therapies or replacements for any one particular tendon.


Author(s):  
Michael B. Albro ◽  
Vikram Rajan ◽  
Clark T. Hung ◽  
Gerard A. Ateshian

Various studies have attempted to quantify the effects of loading on nutrient transport in cartilage and other soft tissues. The application of a dynamic mechanical stimulus has been shown to significantly enhance the mechanical properties of chondrocyte-seeded agarose [1]. While the mechanism for this enhancement is still not completely understood, dynamic loading has been shown theoretically [2] as well as experimentally [3] to increase the uptake of large molecules. Since dextran is available in a wide range of molecular weights and can be conjugated with fluorphores, it has become a popular model system for studying solute transport in statically loaded and free swelling gels and tissues [4, 5]. To better characterize this model system, this study uses fluorescence recovery after photobleaching (FRAP) to investigate the Fickian behavior of linear dextran macromolecules as well as the dependence of its diffusivity on concentration.


Author(s):  
N.K. Bawolin ◽  
W.J. Zhang ◽  
Xiong Biao Chen

The functionality of tissue scaffolds in vivo plays a critical role in the treatment process. Due to the time dependent nature of the mechanical properties of the constituent phases of the scaffold, a wide range of mechanical property histories may be observed during the treatment process, possibly influencing outcomes. The critical nature of the mechanical properties in load bearing applications indicates a need for the simultaneous modelling of both scaffold degradation and tissue regeneration with time, and the resulting effective properties of the tissue engineering construct. To this end, a review of the literature is conducted to identify the various existing approaches to modelling scaffold degradation, tissue behavior, and the dependency of the two processes on one another.


2021 ◽  
Author(s):  
Mikhail Golman ◽  
Adam C Abraham ◽  
Iden Kurtaliaj ◽  
Brittany P Marshall ◽  
Yizhong Jenny Hu ◽  
...  

Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and novel imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.


2018 ◽  
Vol 15 (4) ◽  
pp. 566-571 ◽  
Author(s):  
Araceli Martinez ◽  
Mikhail A. Tlenkopatchev ◽  
Selena Gutierrez

Background: Ring opening metathesis polymerization of lactones using alkylidene catalysts is an alternative to obtain unsaturated linear polyesters with remarkable thermal and mechanical properties. Also, these polyesters have properties of biodegradability which opens up a wide range of applications as environmentally friendly thermoplastics and biomaterials. Objective: This research aims to present one route to obtain an unsaturated linear polyester poly(ω-6- hexadecenlactone) via ring opening-metathesis polymerization of ω-6-hexadecenlactone using the rutheniumalkylidene [Ru(Cl)2(=CHPh)(PCy3)2] (I), [Ru(Cl2)(=CHPh)(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)( PCy3)] (II) and [Ru(Cl2)(=CH(o-isopropoxyphenylmethylene))(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)] (III) and the ruthenium-vinylidene [RuCl2(=C=CH(p-C6H4CF3))(PCy3)2] (IV) catalysts. Conclusion: The high number-average molecular weights of the poly(ω-6-hexadecenlactone) between Mn = 114,800-155,400 g/mol and yields ranging from 96 to 98 % can be achieved by II and III catalysts. The catalysts II and III with the N-heterocyclic carbene ligand showed superior activity and stability upon catalysts I and IV bearing PCy3 ligands. The hydrogenation of poly(ω-6-hexadecenlactone) using Wilkinson catalyst [RhCl(PPh3)3] was studied. The percent crystallinity of the unsaturated poly(ω-6-hexadecenlactone) was 31% with a melting temperature 47.60ºC. Stress-strain measurements of several poly(ω-6-hexadecenlactone) were determined.


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