document
DESCRIPTION
http://dermagraft.odacms3.com/media/files/Waugh.pdfTRANSCRIPT
visit us at www.dermagraft.com
Modeling the Effects of Treating Diabetic Wounds with Engineered Skin SubstitutesWound Repair and Regeneration, Volume 15, 2007
Helen V. Waugh, PhDJonathan A, Sherratt, PhD
•Woundhealingcanonlybeachievedifeitherfibroblastsorhyaluronanareaddedtothewound
•Onceatthewoundsite,fibroblastssynthesizehyaluronanandcollagenandthewoundstartstoheal
•HyaluronanappearstobeakeycomponentinhowDermagraftandApligrafhealdiabeticwounds
key points
100% density (per mm3)
TGF-ß=transforming growth factor-ß; PDGF=platelet derived growth factor
Approximate Healing time
# of Pieces / Application
Frequency of Application
Dermagraft®
Once 1 140 days
Once 8 90 days
Weekly for 8 Wks 1 90 days
2 85 days
3 80 days
Approximate Healing time
# of Pieces / Application
Frequency of Application
Apligraf®
Once 1 No Healing Predicted
Once 5 No Healing Predicted
Weekly for 5 Wks 1 100 days
2 85 days
3 75 days
frequency of application
Component Dermagraft® Apligraf®
Neonatal �broblasts 8000 cells 500 cells
TGF-ß 0.4 pg 4 pg
PDGF 1 pg 1 pg
Collagen 18.75 µg 2 µg
Hyaluronan 80 µg 7.45 µg
The simulation predicted that an 8-week course
of Dermagraft shows wound closure within
approximately 9-10 weeks and 5-week course
of Apligraf heals the wound within approximately
10-11 weeks. Application of a single piece of
Dermagraft shows that healing can be induced,
although the wound does not appear to heal
for several weeks. A single piece of Apligraf
was insufficient to induce wound healing in a
diabetic wound.
Within the context of this model, the key
component to successful healing in diabetic
wounds was found to be hyaluronan. Further,
these therapies were shown to work by increasing
the amount of hyaluronan available in the wound
environment. The time-to-healing results of the
model correlate with those observed in clinical
trials and, thus, the model goes some way to
establishing an understanding of why diabetic
wounds do not heal, and how engineered skin
substitutes affect the diabetic wound environment
to promote wound closure.
In this paper, a novel mathematical model of
wound healing in both normal and diabetic cases
is presented, focusing upon the effects of adding
two currently available commercial engineered
skin substitute therapies to the wound (Apligraf
and Dermagraft). Our work extends a previously
developed model, which considers inflammatory
and repair macrophage dynamics in normal and
diabetic wound healing. Here, we extend the
model to include equations for platelet-derived
growth factor concentration, fibroblast density,
collagen density, and hyaluronan concentration.
This enables us to examine the variation of
these components in both normal and diabetic
wound healing cases, and to model the treatment
protocols of these therapies.
Five Dermagraft application scenarios were
simulated: single piece, 8 pieces as single
treatment, 1 piece a week for 8 weeks, 2 pieces
a week for 8 weeks, and 3 pieces a week for
8 weeks. Similarly, the five Apligraf applications
scenarios were a single piece, 5 pieces as single
treatment, 1 piece a week for 5 weeks, 2 pieces
a week for 5 weeks, and 3 pieces a week for 5
weeks. Individual components of each product
were also used to determine whether they act
alone or synergistically. For this simulation, the
standard approved treatment protocol of 8
weekly applications for Dermagraft and 5 weekly
applications for Apligraf was used, but only one
component was added.
abstract
materials and methods
results conclusions