Traditional wound care strategies, including debridement, moist wound environments, and infection control, remain foundational (Schultz et al. Wound Repair Regen 11(Suppl 1):S1–S28, 2003). The causes of wounds such as arterial or venous in-sufficiency, off- loading or in-proper wound bed preparation should be corrected first. If they may not suffice for challenging wounds adjunctive or innovative modalities could apply. Recent advances in biomaterials, cellular therapy, bioengineering, and biophysical modalities have paved the way for innovative treatments that actively modulate the wound environment to accelerate healing. This chapter explores these novel approaches, evaluates their mechanisms, and examines their clinical relevance.