Porous, resorbable
biomaterials can serve as temporary scaffolds that support cell infiltration, tissue formation, and remodeling of nonhealing skin
wounds. Synthetic
biomaterials are less expensive to manufacture than
biologic dressings and can achieve a broader range of physiochemical properties, but opportunities remain to tailor these materials for ideal host immune and regenerative responses.
Polyesters are a well-established class of synthetic
biomaterials; however, acidic degradation products released by their hydrolysis can cause poorly controlled autocatalytic degradation. Here, we systemically explored
reactive oxygen species (ROS)-degradable polythioketal (PTK)
urethane (UR) foams with varied hydrophilicity for skin wound healing. The most hydrophilic PTK-UR variant, with seven
ethylene glycol (EG7) repeats flanking each side of a thioketal bond, exhibited the highest ROS reactivity and promoted optimal tissue infiltration, extracellular matrix (ECM) deposition, and reepithelialization in porcine skin
wounds. EG7 induced lower
foreign body response, greater recruitment of regenerative immune cell populations, and resolution of type 1
inflammation compared to more hydrophobic PTK-UR scaffolds. Porcine
wounds treated with EG7 PTK-UR foams had greater ECM production, vascularization, and resolution of proinflammatory immune cells compared to
polyester UR foam-based
NovoSorb Biodegradable Temporizing Matrix (BTM)-treated
wounds and greater early vascular perfusion and similar
wound resurfacing relative to clinical gold standard Integra Bilayer
Wound Matrix (BWM). In a porcine ischemic flap excisional
wound model, EG7 PTK-UR treatment led to higher wound healing scores driven by lower
inflammation and higher reepithelialization compared to
NovoSorb BTM. PTK-UR foams warrant further investigation as synthetic
biomaterials for wound healing applications.