''Tissue engineering" uses implanted cells, scaffolds, DNA, protein, and/or
protein fragments to replace or repair injured or diseased tissues and org
ans, Despite its early, success, tissue engineers have faced challenges in
repairing or replacing tissues that serve a predominantly biomechanical fun
ction. An evolving discipline called "functional tissue engineering" (FTE)
seeks to address these challenges. In this paper, the authors present princ
iples of functional tissue engineering that should be addressed when engine
ering repairs and replacements for load-bearing structures. First, in vivo
stress/strain histories need to be measured for a variety of activities. Th
ese in vivo data provide mechanical thresholds that tissue repairs/replacem
ents will likely encounter after surgery, Second, the mechanical properties
of the native tissues must be established for subfailure and failure condi
tions. These "baseline data" provide parameters within the expected thresho
ld for different in vivo activities and beyond these levels if safety facto
rs are to be incorporated. Third, a subset of these these mechanical proper
ties must be selected and prioritized. This subset is important, given that
the mechanical properties of the designs are not expected to completely du
plicate the properties of the native tissues. Fourth, standards must be set
when evaluating the repairs/replacements after surgery so as to deter-mine
"how good is good enough?" Some aspects of the repair outcome may be infer
ior but other mechanical characteristics of the repairs and replacements mi
ght be suitable. New and improved methods must also be developed for assess
ing the function of engineered tissues. Fifth, the effects of physical fact
ors on cellular activity must be determined in engineered tissues. Knowing
these signals may shorten the iterations required to replace a tissue succe
ssfully and direct cellular activity and phenotype toward a desired end goa
l. Finally, to effect a better repair outcome, cell-matrix implants may ben
efit from being mechanically stimulated using in vitro "bioreactors" prior
to implantation Increasing evidence suggests that mechanical stress, as wel
l as other physical factors, may significantly increase the biosynthetic ac
tivity of cells in bioartificial matrices, Incorporating each of these prin
ciples of functional tissue engineering should result in safer and more eff
icacious repairs and replacements for the surgeon and patient. [S0148-0731(
00)00206-5].