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Publication
Porcine Ischemic Wound-Healing Model for Preclinical Testing of Degradable
Biomaterials.
Authors Patil P, Martin JR, Sarett SM, Pollins AC, Cardwell NL, Davidson JM, Guelcher
SA, Nanney LB, Duvall CL
Submitted By Submitted Externally on 7/31/2018
Status Published
Journal Tissue engineering. Part C, Methods
Year 2017
Date Published 11/1/2017
Volume : Pages 23 : 754 - 762
PubMed Reference 28762881
Abstract Impaired wound healing that mimics chronic human skin pathologies is difficult
to achieve in current animal models, hindering testing and development of new
therapeutic biomaterials that promote wound healing. In this article, we
describe a refinement and simplification of the porcine ischemic wound model
that increases the size and number of experimental sites per animal. By
comparing three flap geometries, we adopted a superior configuration
(15?×?10?cm) that enabled testing of twenty 1?cm2 wounds in each animal: 8 total
ischemic wounds within 4 bipedicle flaps and 12 nonischemic wounds. The ischemic
wounds exhibited impaired skin perfusion for ~1 week. To demonstrate the utility
of the model for comparative testing of tissue regenerative biomaterials, we
evaluated the healing process in wounds implanted with highly porous poly
(thioketal) urethane (PTK-UR) scaffolds that were fabricated through reaction of
reactive oxygen species (ROS)-cleavable PTK macrodiols with isocyanates.
PTK-lysine triisocyanate (LTI) scaffolds degraded significantly in vitro under
both oxidative and hydrolytic conditions whereas PTK-hexamethylene diisocyanate
trimer (HDIt) scaffolds were resistant to hydrolytic breakdown and degraded
exclusively through an ROS-dependent mechanism. Upon placement into porcine
wounds, both types of PTK-UR materials fostered new tissue ingrowth over 10 days
in both ischemic and nonischemic tissue. However, wound perfusion, tissue
infiltration and the abundance of pro-regenerative, M2-polarized macrophages
were markedly lower in ischemic wounds independent of scaffold type. The PTK-LTI
implants significantly improved tissue infiltration and perfusion compared with
analogous PTK-HDIt scaffolds in ischemic wounds. Both LTI and HDIt-based PTK-UR
implants enhanced M2 macrophage activity, and these cells were selectively
localized at the scaffold/tissue interface. In sum, this modified porcine
wound-healing model decreased animal usage, simplified procedures, and permitted
a more robust evaluation of tissue engineering materials in preclinical wound
healing research. Deployment of the model for a relevant biomaterial comparison
yielded results that support the use of the PTK-LTI over the PTK-HDIt scaffold
formulation for future advanced therapeutic studies.




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