Engineered human plasma-derived cryogels as a multifunctional scaffold to promote diabetic wound healing

Chronic wounds, characterized by prolonged inflammation and impaired tissue regeneration, represent a critical clinical challenge, particularly in diabetic patients. Conventional therapies often fail to address the multifaceted demands of healing, which requires integrated structural support, bioactive signaling, and immune modulation. To overcome these limitations, we engineered a macroporous cryogel scaffold from methacryloyl-modified human plasma (PlasmaMA) via cryopolymerization. This process transforms the native bioactivity of plasma into a stable, biomimetic extracellular matrix (ECM)-like architecture with tunable mechanical resilience and degradability. The resulting PlasmaMA cryogel inherently retains essential human ECM proteins (e.g., albumin, fibronectin, fibrinogen) and growth factors (e.g., VEGF), which collectively facilitate robust cell adhesion, sustain pro-regenerative signaling, and promote angiogenesis. In vitro, the scaffold demonstrates potent antioxidant activity and attenuates pro-inflammatory responses in macrophages. In a diabetic rat wound model, the PlasmaMA cryogel significantly accelerated wound closure, enhanced collagen deposition and maturation, and improved functional neovascularization compared to scaffolds derived from bovine or human serum albumin. By converging native bioactivity with engineered material properties, the PlasmaMA cryogel creates a pro-healing microenvironment that actively orchestrates tissue repair. This work establishes a versatile human plasma-derived platform as a promising multifunctional therapy for complex wound healing.