Oxygen Diffusion Through Natural Extracellular Matrices: Implications for Estimating Critical Thickness Values in Tendon Tissue Engineering

Oxygen is necessary for maintaining cell proliferation and viability and extracellular matrix (ECM) production in 3-dimensional tissue engineering. Typically, diffusion is the primary mode for oxygen transport in vitro; thus, ensuring an adequate oxygen supply is essential. In this study, we determined the oxygen diffusion coefficients of 3 natural ECMs that are being investigated as construct scaffolds for tendon tissue engineering: small-intestine submucosa (SIS), human dermis (Alloderm (R)), and canine fascia lata. Diffusion coefficients were determined using a standard diffusion cell system. The ranges for each matrix type were: SIS: 7 x 10(-6) - 2 x 10(-5) cm(2)/s, Alloderm (R): 1.9 - 3.1 x 10(-5) cm(2)/s, and canine fascia lata: 1.6 - 4 x 10(-5) cm(2)/s. We used the experimental oxygen diffusivity data for these natural ECMs in a mathematical model of oxygen diffusion through a cell-seeded scaffold to estimate the critical size of cell-seeded scaffold that can be cultured in vitro

An Analytical Model for Rotator Cuff Repairs

Background Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. Methods The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. Findings The validated models predict that load will be distributed ∼ 70–80% to the tendon repair and ∼ 20–30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone–suture–tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct

An Analytical Model for Rotator Cuff Repairs

Background Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. Methods The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. Findings The validated models predict that load will be distributed ∼ 70–80% to the tendon repair and ∼ 20–30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone–suture–tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct

The Biomechanical Role of Scaffolds in Augmented Rotator Cuff Tendon Repairs

Background Scaffolds continue to be developed and used for rotator cuff repair augmentation; however, the appropriate scaffold material properties and/or surgical application techniques for achieving optimal biomechanical performance remains unknown. The objectives of the study were to simulate a previously validated spring-network model for clinically relevant scenarios to predict: (1) the manner in which changes to components of the repair influence the biomechanical performance of the repair and (2) the percent load carried by the scaffold augmentation component. Materials and methods The models were parametrically varied to simulate clinically relevant scenarios, namely, changes in tendon quality, altered surgical technique(s), and different scaffold designs. The biomechanical performance of the repair constructs and the percent load carried by the scaffold component were evaluated for each of the simulated scenarios. Results The model predicts that the biomechanical performance of a rotator cuff repair can be modestly increased by augmenting the repair with a scaffold that has tendon-like properties. However, engineering a scaffold with supraphysiologic stiffness may not translate into yet stiffer or stronger repairs. Importantly, the mechanical properties of a repair construct appear to be most influenced by the properties of the tendon-to-bone repair. The model suggests that in the clinical setting of a weak tendon-to-bone repair, scaffold augmentation may significantly off-load the repair and largely mitigate the poor construct properties. Conclusions The model suggests that future efforts in the field of rotator cuff repair augmentation may be directed toward strategies that strengthen the tendon-to-bone repair and/or toward engineering scaffolds with tendon-like mechanical properties

A new optical system for the determination of deformations and strains: Calibration characteristics and experimental results

Many types of optical strain measurement systems have been used for the determination of deformations and strains in soft biological tissues. The purpose of this investigation is to report a new optical strain measurement system developed in our laboratory which offers distinct advantages over systems developed in the past. Our optical strain system has demonstrated excellent performance in calibration and experimental tests. Calibration tests illustrate the system's accuracy to 0.05% strain at 3.52% strain and 0.18% strain at 11.74% strain. Further, this system can measure strains to within 2% measurement error for strains in a 0-11.74% range when 100 [mu]m increments of motion are used for calibration. The resolution of our system appears to be at least as good as the linear micrometer (2 [mu]m) used as a calibrating standard. Errors in strain measurement due to whole specimen rotation or translation are quantified. Rotations about an in-plane axis perpendicular to the direction of strain and translations in/out of the plane of focus result in the largest sources of error. Finally, in an in vitro biomechanical study of the rabbit Achilles tendon, experimental failure strains are 4.3 +/- 0.9% using this system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31312/1/0000221.pd

Proteoglycans and glycosaminoglycan fine structure in the mouse tail tendon fascicle

The isolated mouse tail tendon fascicle, a functional and homogenous volume of tendon extracellular matrix, was utilized as an experimental system to examine the structure–function relationships in tendon. Our previous work using this model system demonstrated relationships between mean collagen fibril diameter and fascicle mechanical properties in isolated tail tendon fascicles from three different groups of mice (3-week and 8-week control and 8-week Mov13 transgenic) K.A. Derwin, L.J. Soslowsky, J. Biomech. Eng. 121 (1999) 598–604. These groups of mice were chosen to obtain tendon tissues with varying collagen fibril structure and/or biochemistry, such that relationships with material properties could be investigated. To further investigate the molecular details of matrix composition and organization underlying tendon function, we report now on the preparation, characterization, and quantitation of fascicle PGs (proteoglycans) from these three groups. The chondroitin sulfate/dermatan sulfate (CS/DS)-substituted PGs, biglycan and decorin, which are the abundant proteoglycans of whole tendons, were also shown to be the predominant PGs in isolated fascicles. Furthermore, similar to the postnatal maturation changes in matrix composition previously reported for whole tendons, isolated fascicles from 8-week mice had lower CS/DS PG contents (both decorin and biglycan) and a higher collagen content than 3-week mice. In addition, CS/DS chains substituted on PGs from 8-week fascicles were shorter (based on a number average) and richer in disulfated disaccharide residues than chains from 3-week mice. Fascicles from 8-week Mov13 transgenic mice were found to contain similar amounts of total collagen and total CS/DS PG as age-matched controls, and CS/DS chain lengths and sulfation also appeared normal. However, both decorin and biglycan in Mov13 tissue migrated slightly faster on sodium dodecyl sulfate polyacrylamide gel electorphoresis (SDS-PAGE) than the corresponding species from 8-week control, and biglycan from the 8-week Mov13 fascicles appeared to migrate as a more polydisperse band, suggesting the presence of a unique PG population in the transgenic tissue. These observations, together with our biomechanical data [Derwin and Soslowsky, 1999] suggest that compensatory pathways of extracellular matrix assembly and maturation may exist, and that tissue mechanical properties may not be simply determined by the contents of individual matrix components or collagen fibril size. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34919/1/1100190216_ftp.pd

Oxygen Diffusion Through Natural Extracellular Matrices: Implications for Estimating Critical Thickness Values in Tendon Tissue Engineering

Oxygen is necessary for maintaining cell proliferation and viability and extracellular matrix (ECM) production in 3-dimensional tissue engineering. Typically, diffusion is the primary mode for oxygen transport in vitro; thus, ensuring an adequate oxygen supply is essential. In this study, we determined the oxygen diffusion coefficients of 3 natural ECMs that are being investigated as construct scaffolds for tendon tissue engineering: small-intestine submucosa (SIS), human dermis (Alloderm (R)), and canine fascia lata. Diffusion coefficients were determined using a standard diffusion cell system. The ranges for each matrix type were: SIS: 7 x 10(-6) - 2 x 10(-5) cm(2)/s, Alloderm (R): 1.9 - 3.1 x 10(-5) cm(2)/s, and canine fascia lata: 1.6 - 4 x 10(-5) cm(2)/s. We used the experimental oxygen diffusivity data for these natural ECMs in a mathematical model of oxygen diffusion through a cell-seeded scaffold to estimate the critical size of cell-seeded scaffold that can be cultured in vitro

Improved time-zero biomechanical properties using poly-L-lactic acid graft augmentation in a cadaveric rotator cuff repair model

Rotator cuff repair failure rates range from 20% to 90%, and failure is believed to occur most commonly by sutures cutting through the tendon due to excessive tension at the repair site. This study was designed to determine whether application of a woven poly-L-lactic acid device (X-Repair; Synthasome, San Diego, CA) would improve the mechanical properties of rotator cuff repair in vitro. Eight pairs of human cadaveric shoulders were used to test augmented and non-augmented rotator cuff repairs. Initial stiffness, yield load, ultimate load, and failure mode were compared. Yield load was 56% to 92% higher and ultimate load was 56% to 76% higher in augmented repairs. No increase in initial stiffness was found. Failure by sutures cutting through the tendon was reduced, occurring in 17 of 20 non-augmented repairs but only 7 of 20 augmented repairs. Our data show that application of the X-Repair device significantly increased the yield load and ultimate load of rotator cuff repairs in a human cadaveric model and altered the failure mode but did not affect initial repair stiffness

An Analytical Model for Rotator Cuff Repairs

Background: Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. Methods: The individual components of the repair constructs were modeled as non-linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. Findings: The validated models predict that load will be distributed ~70-80% to the tendon repair and ~20-30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone-suture-tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct

Exploratory study on the effect of osteoactivin on muscle regeneration in a rat volumetric muscle loss model - Fig 2

<p>Representative sections of gels before (<b>A</b>, <b>B</b>) and after 5 days (<b>B</b>-<b>E</b>) in vitro incubation showed OA was detected in gels in both low OA (<b>A</b>, <b>C</b>) and high OA (<b>B</b>, <b>D</b>) groups while no OA in gel only group (<b>E</b>) Before and after incubation, the amount of OA in the high OA group (<b>B</b>, <b>D</b>) appeared higher than that in the low OA group (<b>A</b>, <b>C</b>). The amount of OA in each low or high OA group after incubation appeared to be similar in the gels before incubation. Scale bar = 2 mm applies to all images.</p