(203b) Injectable Polyurethane Composite Scaffolds Delay Wound Closure and Support Cellular Infiltration and Remodeling In Rat Excisional Wounds

Injectable scaffolds present compelling opportunities for wound
repair and regeneration due to their abilities to fill irregularly shaped
defects and deliver biologics such as growth factors. However, there are
several challenges that must be overcome, including toxicity of reactants or
intermediates, curing in a reasonable amount of time, forming a sufficient pore
structure, and achieving robust mechanical properties.  In this study, we investigated the properties
of injectable polyurethane (PUR) biocomposite scaffolds and their application
in cutaneous wound repair using a rat excisional model. PUR scaffolds were
synthesized by reacting a lysine triisocyanate-poly(ethylene
glycol) prepolymer with a polysaccharide filler (hyaluronic acid [HA] or
carboxymethyl cellulose [CMC]) and a polyester triol with a backbone comprising
60% caprolactone, 30% glycolide, and 10% lactide.
 Cure profiles of the scaffolds were
measured using a rheometer, thermal transitions were evaluated by differential
scanning calorimetry, and mechanical properties were measured using a dynamic
mechanical analyzer. The reactivities of polyester triol, HA, CMC, and water
with LTI-PEG were determined using attenuated total reflectance-fourier
transform infrared spectroscopy. The capacity of the scaffolds to facilitate
dermal wound healing was evaluated in an excisional wound model in
Sprague-Dawley rats. The groups investigated were blank wounds, PUR scaffolds
with 15 wt% HA, and PUR scaffolds with 15% CMC. 
Wounds were harvested at days 7, 17, 26, and 35 (n = 4) and processed
for histological evaluation.  Hematoxylin
& eosin, Gomori's trichrome, picrosirius red, TUNEL, Ki67, a-SMA, and procollagen I immunostaining were
performed on the tissue sections. The scaffolds have a minimal reaction exotherm
(<10°C), a working time of 6-7 min, and a setting time of 16-19 min.  Moreover, the compressive Young's modulus of
the scaffolds under physiologic conditions ranges from 30-60 kPa, which is
comparable to that of human skin.  In the rat
excisional wound model, injection of settable biocomposite scaffolds stented
the wounds at early time points, resulting in a regenerative rather than a
scarring phenotype at later time points. Measurements of wound length and
thickness revealed that the treated wounds were less contracted at day 7
compared to blank wounds. Analysis of cell proliferation and apoptosis showed
that the scaffolds were biocompatible and supported tissue ingrowth. Furthermore,
the number of Ki67+ cells in the PUR scaffolds was significantly higher than in
the blank wounds from days 17 ? 26.  Myofibroblast
formation and collagen organization provided evidence that the scaffolds have a
positive effect on extracellular matrix remodeling by disrupting the formation
of an aligned matrix under elevated tension. In summary, we have developed an
injectable biodegradable polyurethane biocomposite scaffold that enhances
cutaneous wound healing in a rat model.