Human-derived acellular matrices for dermal replacement - Biomaterials for Treating Skin Loss - page 163

Sclafani et al ., 2000). These biological properties have translated to successful use
in reconstructive surgery and soft tissue augmentation (Homicz & Watson, 2004;
Karpenko et al ., 2003; Maloney et al. , 2004).
Standard care for a chronic wound generally follows the paradigm established
for acute wounds with only minor alterations (Schultz et al ., 2003). A chronic
wound results when the normal healing process is disrupted and represents an even
more challenging clinical problem (Lazarus et al ., 1994). However, a chronic
wound presents a significantly different biochemical and cellular environment,
particularly with respect to the presence of necessary growth factors required for
healing. Furthermore, the accumulation of excess chronic fluid in the wound may
actually retard wound closure (Tarnuzzer & Schultz, 1996; Trengove et al. , 2000).
These wounds exhibit elevated levels of matrix protease activity (Xue et al. , 2006)
which adversely affect provisional matrix integrity (Grinnell et al. , 1992) and
promote an imbalance in matrix metabolism (Trengove et al ., 1999). All these
factors result in the inability of the local environment to facilitate satisfactory
healing of the wound.
The medical costs associated with chronic wounds as well as the detrimental
effects that chronic wounds have on a patient's quality of life are well established.
Most advanced therapeutic treatments, such as recombinant PDGF and skin
equivalents, unfortunately require multiple applications to achieve wound resolu-
tion. However, in a pilot study of 40 patients, a single application of RTM
eliminated the need for skin grafting and demonstrated statistically faster wound
closure compared to standard debridement and dressing care protocols ( Fig. 10.12 )
(Brigido et al. , 2004). Continued monitoring of patients in this prospective,
controlled, randomized trial showed 85% of the patients treated with a single
application of RTM had wound closure by 16 weeks compared to 28% in the
standard care control group (Brigido, 2006). These results are consistent with a
retrospective analysis of deep wound healing in diabetic patients, where 82% of
patients' wounds treated with a single application of RTM healed during the 20-
week evaluation and represented a mean wound duration of just less than 9 weeks
(Martin et al ., 2005).

10.5 Universality of acellular regenerative tissue

matrices for soft tissue replacement

The preclinical and clinical successes described above reflect the ability of an
acellular RTM to support tissue regeneration by providing the biochemical and
structural environments for wounds that are required to support host
recellularization and vascularization. However, these studies demonstrate only
the beginning of RTM utility. The clinical need for an ECM material that
supports the intrinsic regenerative process has driven the use of RTMs for new
indications.