Biomedical Engineering Reference
In-Depth Information
However, quantitative measurements of pore volume fraction or average pore size
have been rarely, if ever, reported in this field.
Next, we consider the effect of degradation rate of the acellular matrix. In stud-
ies with decellularized matrices, degradation of the acellular matrix has been often
associated with the extent of new tissue deposition by the host, an example of a
remodeling process (e.g., Valentin et al. 2006). In other cases, a quantitative study
of degradation of the implant showed that the byproducts of the degradation process
enter the circulation and are rapidly removed via urinary excretion (Record et al.
2001; Gilbert et al. 2007).
In a study of Achilles tendon regeneration, it was necessary to determine the
degradation rate in order to assess the load-bearing function of the regenerated ten-
don tissue (Gilbert et al. 2007). Quantitative methodology based on isotope labeling
of the implant was developed for measuring the degradation rate of the acellular
matrix (Record et al. 2001; Gilbert et al. 2007). The half-life of the porcine small
intestinal mucosa was determined to be about 20 days when implanted at the canine
urinary bladder site (Record et al. 2001). At a different anatomical site, the canine
Achilles tendon, the half-life of the same acellular matrix was determined to be also
about 20 days (Gilbert et al. 2007). This important finding suggests the possibility
that the half-life of the implant is independent of anatomical site, a speculative hy-
pothesis that increases the importance of this scaffold parameter. The value of half-
life measurement for the small intestinal submucosa (Record et al. 2001; Gilbert
et al. 2007) coincides with the optimal half-life for collagen matrices, 2 ± 1 weeks,
used to regenerate skin (Yannas and Burke 1980; Yannas et al. 1989) and peripheral
nerves (Soller et al. 2012). This quantitative agreement between two independent
laboratories, using different scaffolds, is striking and encourages pursuit of further
measurement of degradation rate in studies of regeneration.
We now turn to the effect of surface chemistry. Decellularized matrices mostly
consist of extracellular matrix, and the latter consists mostly of collagen. At least
one analytical study determined over 90 % wt. collagen, mostly type I, in small in-
testinal submucosa, the most commonly used acellular matrix (Badylak et al. 2009).
Collagens of other types were also detected in this study, together with a variety of
GAGs, such as chondroitin sulfate, heparin sulfate, and hyaluronic acid (Badylak
et al. 2009).
Direct evidence that insoluble type I collagen, free of other macromolecules in-
cluding glycosaminoglycans, has regenerative activity in peripheral nerve studies
has been reported recently (Soller et al. 2012). A library of GAG-free collagen tubu-
lar scaffolds was implanted in the transected peripheral nerve and the result showed
that collagen alone, if properly structured with respect to pore size and degradation
rate, led to very high quality of regeneration at 9 weeks across a gap of 15 mm in
the rat sciatic nerve (Soller et al. 2012).
Investigators working with decellularized matrices have apparently not consid-
ered seriously the possibility that the collagen surface itself is a potentially active
component in their acellular scaffolds. Recent evidence (Tzeranis 2013; Tzeranis
et al. 2010, 2014) has shown that the surface of a temporarily insoluble collagen
