Biomedical Engineering Reference
In-Depth Information
composition and architecture and endowed with the necessary mechanical proper-
ties, has the potential to orchestrate a regenerative process resulting in little or no
scarring. It is for these reasons that a naturally occurring, structurally preserved
ECM template provided the rationale for the development of the acellular dermal
matrix as a regenerative tissue matrix.
10.2
Processing native tissues
10.2.1
Acellular dermal matrix as an RTM
LifeCell's RTMs AlloDerm, GraftJacket and Repliform are produced from allo-
graft skin procured by banks accredited by the American Association of Tissue
Bank (AATB) and in compliance with 21CFR1271. The skin is quarantined
until donor medical/social histories and serology testing is complete. Once
medical release is obtained, the RTMs are manufactured through a combination
of proprietary processes necessary for antigenic epitope removal and stable
preservation.
The initial LifeCell processing steps remove the cellular components, eliminat-
ing the antigens that would normally promote clinically relevant inflammatory or
immunologic responses. The epidermis is next detached by agitation in solutions
that modulate ionic strength, pH and divalent cation concentration. These non-
enzymatic steps separate the cellular epidermis without proteolytic cleavage of the
underlying basement membrane. In this manner, the components of the structure,
including laminin and collagen types IV and VII are retained intact. The remaining
cellular material of the dermis and dermal vasculature are solubilized by low
molecular weight detergents. During these steps, specialized buffers are employed
to prevent degradation and promote preservation of the principal ECM compo-
nents collagen type I, elastin and various glycosaminoglycans.
Once the acellular RTM is prepared, it must be preserved such that it can be
delivered to the clinician with retention of its biologic function. The core technologic
requirement and the basis for stable preservation is controlling formation and
growth of ice crystals during freeze-drying of the matrix. Biocompatible cryo- and
lyoprotectants are introduced into the matrix to promote and support amorphous
ice formation. Successfully controlling ice formation minimizes damage to the
matrix during the freeze-drying process (Fig. 10.1) and LifeCell's drying protocols
have been developed based upon the thermodynamic and kinetic stability charac-
teristics of the frozen matrix to prevent damage in the final dried product.
LifeCell's RTM materials are processed aseptically without terminal sterilization
which can induce detrimental damage to the matrix. This mild and minimal
processing results in preserving both the biochemical components and the under-
lying structural architecture inherent in the ECM that is ultimately necessary for a
functional RTM. Rehydration of the RTM yields a material that is flexible and
capable of being shaped, cut and sutured depending upon the specific application
