INTRODUCTION: Soft tissue losses from aging, trauma, or congenital malformation affect millions of people each year. Injectable fillers are effective in providing soft tissue volumization for facial rejuvenation and reconstruction. The majority of dermal fillers are based on hyaluronic acid (HA) and rely on high concentrations of HA to provide adequate viscosity and temporary persistence. This results in poor cellular infiltration, inflammation, and granuloma formation. To address these deficits, we have developed a unique dermal filler based on a nanofiber-hydrogel composite with interfacial bonding that mechanically mimics native fat. The composite structure allows cellular infiltration while also enabling longer lasting restoration with less inflammation and fibrosis.
METHODS: We have developed a new dermal filler by interfacially bonding biodegradable poly(caprolactone) fibers with hyaluronic acid hydrogel, forming an integrated structure resembling the architecture and mechanical properties of adipose tissue. To optimize cellular infiltration of our filler, we cultured human adipose-derived stem cells (hASCs) within our nanofiber-hydrogel composite and investigated cell migration and vascularization in vitro [3]. We then subcutaneously delivered our nanofiber-hydrogel composite filler into the backs of Lewis rats to assess the biocompatibility, shape retention, and host tissue integration
RESULTS: HASCs had the longest migration and highest density of vascular-like network formation within the nanofiber-hydrogel composite compared to hydrogel-only controls in vitro. In the rat model, the nanofiber-hydrogel composite filler exhibited no signs of inflammation or infection. At three months, the composite filler had greater shape retention and less foreign body reaction compared to commercial dermal fillers. Additionally, our composite filler had superior integration with the host tissue with a significantly higher density of blood vessel ingrowth.
CONCLUSION: We developed a cutting-edge dermal filler that provides long-lasting shape retention with superior host integration. This platform holds high potential for clinical translation to improve soft-tissue restoration. Additionally, the technology developed here sets a solid foundation for the future development of stem cell-based therapies and drug delivery.