Biomedical Engineering Reference
In-Depth Information
tissue repair, the suture pullout strength of 1 kg has been found to be adequate for arthroscopically
assisted surgery in simulated placement procedures in human cadaver knees, and this suture pullout
strength should be maintained as the minimal strength required for this particular application.
6.3.6 Hydrophilicity
Hydration of an implant facilitates nutrient diffusion. The extent of hydration would also provide infor-
mation on the space available for tissue ingrowth. The porous collagen matrix is highly hydrophilic and
therefore facilitates cellular ingrowth. The biomechanical properties of the hydrophilic collagen matrix
such as fluid outflow under stress, fluid inflow in the absence of stress, and the resiliency for shock
absorption are the properties also found in the weight-bearing cartilagenous tissues.
6.3.7 Permeability
The permeability of ions and macromolecules is of primary importance in tissues that do not rely on
vascular transport of nutrients to the end organs. The diffusion of nutrients into the interstitial space
ensures the survival of the cells and their continued ability of growth and synthesis of tissue-specific
extracellular matrix. Generally, the permeability of a macromolecule the size of the bovine serum albu-
min (MW 67,000) can be used as a guideline for probing accessibility of the interstitial space of a col-
lagen template (Li et al., 1994).
6 . 3 . 7. 1
In Vivo
Stability
As stated above, the rate of template resorption and the rate of new tissue regeneration have to be bal-
anced so that the adequate mechanical properties are maintained at all times. The rate of
in vivo
resorp-
tion of a collagen-based implant can be controlled by controlling the density of the implant and the
extent of intermolecular crosslinking. The lower the density, the greater the interstitial space and gener-
ally the larger the pores for cell infiltration, leading to a higher rate of matrix degradation. The control
of the extent of intermolecular crosslinking can be accomplished by using bifunctional crosslinking
agents under conditions that do not denature the collagen. Glutaraldehyde, formaldehyde, adipyl chlo-
ride, hexamethylene diisocyanate, and carbodiimides are among the many agents used in crosslinking
the collagen-based implants. Crosslinking can also be achieved through vapor phase of a crosslinking
agent. The vapor phase crosslinking is effective in crosslinking agents of high vapor pressures such
as formaldehyde and glutaraldehyde. The vapor crosslinking is particularly useful for thick implants
of vapor-permeable dense fibers where crosslinking in solution produces nonuniform crosslinking. In
addition, intermolecular crosslinking can be achieved by heat treatment under high vacuum. This treat-
ment causes the formation of an amide bond between an amino group of one molecule and the car-
boxyl group of an adjacent molecule and has often been referred to in the literature as dehydrothermal
crosslinking.
The shrinkage temperature of the crosslinked matrix has been used as a guide for
in vivo
stability of
a collagen implant (Li, 1988). The temperature of shrinkage of collagen fibers measures the transition of
the collagen molecules from the triple helix to a random coil conformation. This temperature depends
on the number of intermolecular crosslinks formed by chemical means. Generally, the higher the num-
ber of intermolecular crosslinks, the higher the thermal shrinkage temperature and more stable the
material
in vivo
.
A second method of assessing the
in vivo
stability is to determine the crosslinking density by applying
the theory of rubber elasticity to denatured collagen (Wiederhorn and Beardon, 1952). Thus, the
in vivo
stability can be directly correlated with the number of intermolecular crosslinks introduced by a given
crosslinking agent.
Another method that has been frequently used in assessing the
in vivo
stability of a collagen-based
implant is to conduct an
in vitro
collagenase digestion of a collagen implant. Bacterial collagenase is
