Polyphosphate-crosslinked hydrogels: structural design and bioactivity for tissue engineering scaffolds.

Infected chronic wounds present complex pathophysiology characterized by persistent bacterial colonization and impaired tissue regeneration, necessitating multifunctional biomaterials for integrated therapeutic intervention. This study developed a polyphosphate-crosslinked hydrogel system via zinc ion-mediated crosslinking of sodium polyphosphate and sodium alginate, with co-loading of ampicillin and transforming growth factor-β1 (TGF-β1). The hydrogel achieved loading efficiencies of 85.2 ± 2.5% for ampicillin and 78.6 ± 1.2% for TGF-β1, with optimized swelling properties and mechanical characteristics suitable for soft tissue engineering. In vitro evaluations demonstrated potent bactericidal activity against Escherichia coli with bacterial load reduction exceeding 4 log10 CFU mL-1 within 24 hours, enhanced human dermal fibroblast proliferation to 222.5% at 96 hours, and significant anti-senescence efficacy with SA-β-gal-positive cells reduced to 24.2%. Mechanistically, the therapeutic effects were attributed to complementary actions where ampicillin eliminated bacterial threats while TGF-β1 promoted fibroblast proliferation, collagen synthesis, and inflammatory resolution. This multifunctional scaffold platform demonstrates promising potential for advanced wound management, including applications in wound dressings, burn treatment, and tissue regeneration.