Chiral multilevel-structured hydroxyapatite nano-bacterial cellulose membrane with anti-inflammatory activity and regulation of immune microenvironment promotes wound healing in the elderly

Cutaneous wound healing in the elderly is impaired by persistent inflammation and immune dysregulation. The chirality of materials has been shown to modulate wound healing efficacy. However, the translational potential of chiral-engineered biomaterials for wound dressing applications remains underexplored. In this study, we developed Chiral multilevel-structured hydroxyapatite nano-bacterial cellulose membrane (CMHAp@BC), a novel biomaterial, significantly modulates the innate immune response to accelerate aging skin full-thickness wound healing. Notably, levorotatory CMHAp@BC (L-CHB) demonstrated superior performance over other chiral forms (D-, rac-, and achiral variants) in comprehensively promoting wound healing by attenuating neutrophil infiltration and directing macrophage polarization toward regenerative phenotypes. Through evaluation in natural aging and severe combined immunodeficient murine models, we establish that L-CHB exerts multifunctional therapeutic effects by suppressing bacterial colonization, attenuating neutrophil recruitment through NF-κB pathway inhibition, and promoting a favorable shift toward M2 macrophage polarization. These findings underscore the potential of L-CHB to establish a regenerative immune microenvironment, thereby offering a promising strategy for advanced wound care. • First chiral dressing: L-CHB suppresses neutrophils via NF-κB inhibition and induces M2 macrophage polarization. • Targets geriatric immune dysregulation by attenuating neutrophil hyperactivation and controlling macrophage phenotypic polarization. • Efficacy confirmed in natural aging and severe combined immunodeficient models, proving innate immunity-dependent action.