Soft tissue reconstruction often requires multiple surgical procedures that can
result in scars and disfiguration. Facial soft tissue reconstruction represents a clinical
challenge because even subtle deformities can severely affect an individual’s
social and psychological function. We therefore developed a biosynthetic soft tissue
replacement composed of poly(ethylene glycol) (PEG) and hyaluronic acid (HA) that can be
injected and photocrosslinked in situ with transdermal light exposure. Modulating the
ratio of synthetic to biological polymer allowed us to tune implant elasticity and volume
persistence. In a small-animal model, implanted photocrosslinked PEG-HA showed a
dose-dependent relationship between increasing PEG concentration and enhanced implant
volume persistence. In direct comparison with commercial HA injections, the PEG-HA
implants maintained significantly greater average volumes and heights. Reversibility of
the implant volume was achieved with hyaluronidase injection. Pilot clinical testing in
human patients confirmed the feasibility of the transdermal photocrosslinking approach for
implantation in abdomen soft tissue, although an inflammatory response was observed
surrounding some of the materials.
Poly(ethylene glycol) (PEG)-based hydrogels are extensively used in a variety of biomedical applications due to ease of synthesis and tissue-like properties. Recently, there have been varied reports regarding PEG hydrogel’s degradation kinetics and in vivo host response. In particular, these studies suggest that the surrounding tissue environment could play a critical role in defining the inflammatory response and degradation kinetics of PEG implants. In the present study we demonstrated a potential mechanism of PEG hydrogel degradation, and in addition we show potential evidence of the role of the surrounding tissue environment on producing variable inflammatory responses.
The rat subcutis model demonstrated the ability to differentiate between HA fillers with different residence times. The caliper-based rat-subcutis method demonstrated consistent volumetric analysis and correlated with human residence times of HA fillers. These quantitative results validate the rat subcutis model as an expedited preclinical model for HA fillers.
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