Design and evaluation of ionically crosslinked multifunctional ELP-SA composite hydrogels for 3D cell culture

Hydrogels are 3D crosslinked polymeric networks that can absorb and retain substantial quantities of water or biological fluids. Their soft, hydrated nature and adjustable properties render them highly suitable for a range of biomedical applications, such as drug delivery, tissue engineering and wound healing, by emulating the extracellular matrix. To overcome the limitations associated with the mechanical properties and biological functions of conventional elastin-like polypeptide (ELP) and sodium alginate (SA) hydrogels, a novel ion-responsive two-component ELP-SA hydrogel was developed. ELP variants with functional modules (ELPK/ELPR/ELPS/ELPL) were engineered through genetic techniques and purified to a high degree of purity (>95%) using high-salt-reversible phase-change technology. The release of Ca²⁺ from gluconolactone simultaneously initiated ELP self-assembly and SA ion crosslinking, resulting in the formation of an injectable composite gel within 10 min. This material demonstrated enhanced mechanical properties (storage modulus G' 450-1773 Pa, pore size 52-103 μm) and reduced swelling (decreased to 60% of that of the SA hydrogel). Functionally, ELPR improved cell adhesion (1.42 times that of collagen I), ELPS facilitated angiogenesis (1.32 times higher than that of the positive control), and ELPL achieved an antibacterial rate exceeding 98% and induced macrophage M2 polarization. This supports the growth of 3D cell spheroids (survival rate of >95%). This modular design synergistically integrates mechanical strength with diverse biological activities, providing an intelligent dressing solution with antibacterial, healing, and anti-inflammatory properties for treating chronic wounds.