Role of Biomechanics in Functional Tissue Engineering

2004 ◽  
Vol 844 ◽  
Author(s):  
Kai-Nan An

ABSTRACTFunctional tissue engineering establishes functional criteria for design and manufacture of the scaffold matrix for repair and replacement. It also provides useful and strategic information in mechanical stimulation of the cells seeded in the matrix before and after surgical placement to enhance the success of tissue engineering. Biomechanics plays an important role in accomplishing these requirements by assessing the in vivo environment and the material properties.

Author(s):  
X. Edward Guo ◽  
Helen H. Lu ◽  
Morakot Likhitpanichkul ◽  
Van C. Mow

2000 ◽  
Vol 122 (6) ◽  
pp. 570-575 ◽  
Author(s):  
David L. Butler ◽  
Steven A. Goldstein ◽  
Farshid Guilak

“Tissue engineering” uses implanted cells, scaffolds, DNA, protein, and/or protein fragments to replace or repair injured or diseased tissues and organs. Despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function. An evolving discipline called “functional tissue engineering” (FTE) seeks to address these challenges. In this paper, the authors present principles of functional tissue engineering that should be addressed when engineering repairs and replacements for load-bearing structures. First, in vivo stress/strain histories need to be measured for a variety of activities. These in vivo data provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery. Second, the mechanical properties of the native tissues must be established for subfailure and failure conditions. These “baseline data” provide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated. Third, a subset of these mechanical properties must be selected and prioritized. This subset is important, given that the mechanical properties of the designs are not expected to completely duplicate the properties of the native tissues. Fourth, standards must be set when evaluating the repairs/replacements after surgery so as to determine, “how good is good enough?” Some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might be suitable. New and improved methods must also be developed for assessing the function of engineered tissues. Fifth, the effects of physical factors on cellular activity must be determined in engineered tissues. Knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal. Finally, to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro “bioreactors” prior to implantation. Increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices. Incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient. [S0148-0731(00)00206-5]


Author(s):  
David L. Butler ◽  
Natalia Juncosa-Melvin ◽  
John West ◽  
Jason Shearn ◽  
Marc Galloway ◽  
...  

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.


2000 ◽  
Author(s):  
David L. Butler

Abstract Clinicians, biologists, and engineers face difficult challenges in engineering effective, cell-based composites for repair of orthopaedic and cardiovascular tissues. Whether repairing articular cartilage, bone, or blood vessel, the demands placed on the surgical implants can threaten the long-term success of the procedure. In 1998, the US National Committee on Biomechanics addressed this problem by suggesting a new paradigm for tissue engineering called “functional tissue engineering” or FTE. FTE seeks to address several important questions. What are the biomechanical demands placed upon the normal tissue and hence the tissue engineered implant after surgery? What parameters should a tissue engineer design into the implant before surgery? And what biomechanical parameters should the tissue engineer track to determine if the resulting repair is successful? To illustrate the principles, this presentation will discuss tendon repair as a model system for functional tissue engineering.


2007 ◽  
Vol 292 (4) ◽  
pp. E1000-E1009 ◽  
Author(s):  
Bret M. Windsor-Engnell ◽  
Etsuko Kasuya ◽  
Masaharu Mizuno ◽  
Kim L. Keen ◽  
Ei Terasawa

We have previously shown that a decrease in γ-aminobutyric acid (GABA) tone and a subsequent increase in glutamatergic tone occur in association with the pubertal increase in luteinizing hormone releasing hormone (LHRH) release in primates. To further determine the causal relationship between developmental changes in GABA and glutamate levels and the pubertal increase in LHRH release, we examined monkeys with precocious puberty induced by lesions in the posterior hypothalamus (PH). Six prepubertal female rhesus monkeys (17.4 ± 0.1 mo of age) received lesions in the PH, three prepubertal females (17.5 ± 0.1 mo) received sham lesions, and two females received no treatments. LHRH, GABA, and glutamate levels in the stalk-median eminence before and after lesions were assessed over two 6-h periods (0600–1200 and 1800–2400) using push-pull perfusion. Monkeys with PH lesions exhibited external signs of precocious puberty, including significantly earlier menarche in PH lesion animals (18.8 ± 0.2 mo) than in sham/controls (25.5 ± 0.9 mo, P < 0.001). Moreover, PH lesion animals had elevated LHRH levels and higher evening glutamate levels after lesions, whereas LHRH changes did not occur in sham/controls until later. Changes in GABA release were not discernible, since evening GABA levels already deceased at 18–20 mo of age in both groups and morning levels remained at the prepubertal levels. The age of first ovulation in both groups did not differ. Collectively, PH lesions may not be a good tool to investigate the mechanism of puberty, and, taking into account the recent findings on the role of kisspeptins, the mechanism of the puberty onset in primates is more complex than we initially anticipated.


2004 ◽  
Vol 427 ◽  
pp. S190-S199 ◽  
Author(s):  
David L Butler ◽  
Jason T Shearn ◽  
Natalia Juncosa ◽  
Matthew R Dressler ◽  
Shawn A Hunter

Author(s):  
Savio L.-Y. Woo ◽  
Alejandro J. Almarza ◽  
Sinan Karaoglu ◽  
Steven D. Abramowitch

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