(684b) Injectable, Biodegradable, Polyurethane Scaffolds for Dermal Wound Healing & Tissue Regeneration

Numerous synthetic and biological scaffolds show promise for wound repair and tissue regeneration, but few have the capacity to cure in situ. An injectable formulation could facilitate minimally invasive surgical procedures and allow customization at the time of implantation, including conforming to irregular wound dimensions and delivering biologicals to enhance the wound repair response.

We have developed highly porous, biodegradable, polyurethane (PUR) scaffolds that support cellular infiltration, new tissue formation, degrade to non-cytotoxic products, and elicit minimal inflammation. Their elastomeric, resilient properties may promote thorough contact with wound boundaries. Considerations taken into account include optimizing the injectability, addressing cure time, material-tissue adhesion, reaction temperature profile, and limiting possible monomer toxicity. These scaffolds would ideally support regeneration of both form and function of wounds in a range of tissues.

Injectable PUR scaffolds were synthesized by syringe-mixing of two phases: a prepolymer of lysine triisocyanate (LTI) and 200-MW PEG, and a hardener consisting of a polyester triol, water, catalyst, and pore opener. Hyaluronic acid (HA) particles were added to the prepolymer at 15-wt% to absorb excess moisture in the wound area and perhaps enhance healing. The reactive liquid mixture was applied directly into 8-mm excisional dermal wounds in male Sprague-Dawley rats, and expanded by gas foaming to fill the defects. The adherence and permeability of the scaffolds were evaluated after injecting and curing in situ, and the water, catalyst, pore opener concentrations were adjusted to achieve curing times practical for clinical applications. The scaffolds were assessed for biocompatibility, biodegradation, cellular infiltration, and tissue regeneration. Ongoing experiments include assessment of long-term biocompatibility and regenerative capacities of the injected scaffolds. Mechanical properties were also ascertained by dynamic mechanical analysis (DMA).

After a mixing time of 2 min, the formulation allowed 5 min of working time. The scaffolds had an average rise time 8 ? 10 minutes, with an internal reaction temperature maximum of 41 ºC. At 87% porosity, the elastomeric scaffolds exhibit a Young's modulus of 75 kPa & compressive stress of 46 kPa, which can be increased with higher HA content. Trichrome histology showed rapid material biodegradation with mononuclear cell infiltration leading to early granulation tissue by day 4. Collagen deposition and new tissue organization proceeded, and by day 11 material remnants were transiently engulfed by giant cells. Mature granulation tissue and almost complete reepithelization was present by day 18, accompanied by evidence of folliculogenesis in the neoepidermis, a phenomenon that may indicate regeneration and limited scarring. Hyaluronic acid inclusion in the scaffolds improved adhesion between the material and wound bed by absorbing excess moisture, and its presence may have augmented the local healing response.

These biodegradable, tunable PUR materials demonstrate potential as a template for regeneration of skin and potentially other soft tissues, with strength and material properties tunable for a specific application. To optimize the injectability, the isocyanate was re-formulated as an LTI-PEG prepolymer in order to avoid any possible monomeric isocyanate toxicity. In addition to providing a template for tissue regeneration, biologicals?including growth factors, antibiotics, small-molecule drugs?also may be incorporated in the scaffolds to enhance healing.