Enhanced wound healing potential of a carboxymethyl cellulose/gelatin-based hydrogel containing decellularized amniotic membrane and Matricaria chamomilla extract: A multifunctional composite dressing

Chronic wound healing remains a complex biological process influenced by excessive inflammation, oxidative stress, microbial invasion, and insufficient tissue regeneration. Therefore, the design of multifunctional biomaterials that integrate structural support with biological regulation has emerged as a promising strategy in advanced wound care. This study sought to develop a composite hydrogel incorporating decellularized amniotic membrane (dAM)-derived extracellular matrix components alongside Matricaria chamomilla extract, with the goal of achieving enhanced regenerative and therapeutic outcomes.

A CMC/GEL-Chamomilla-dAM hydrogel was prepared using decellularized dAM and subsequently evaluated in terms of its physicochemical and biological characteristics. The effectiveness of the decellularization process and preservation of ECM components were first examined, followed by characterization of hydrogel morphology, rheological properties, swelling and degradation behavior, and pH stability. Its biological performance was further assessed through hemocompatibility, cytocompatibility, antioxidant, anti-inflammatory, and antibacterial assays, as well as a full-thickness wound model.

Incorporation of dAM and chamomile extract resulted in a stable hydrogel with favorable physicochemical and biological characteristics. The decellularization procedure removed 97.9% of the DNA. The resulting composite hydrogel exhibited an average pore size of 78.3 ± 9.8 µm, and all hydrogel formulations showed hemolysis rates below the 5% threshold accepted for blood-contacting biomaterials, with values ranging from 3.8% to 4.5%. The composite hydrogel also supported enhanced fibroblast viability (109.6 ± 11.3%) and demonstrated antioxidant, anti-inflammatory, and antibacterial activities against wound-associated pathogens. In vivo, treatment with CMC/GEL-Chamomilla-dAM accelerated wound closure (85.7 ± 6.3% at day 14) and supported tissue regeneration, outperforming both the dAM-containing hydrogel (78.9 ± 9.9%) and the commercial DuoDERM dressing (58.9 ± 4.5%), as evidenced by improved re-epithelialization, collagen deposition, angiogenesis, and early signs of tissue remodeling.

The CMC/GEL-Chamomilla-dAM hydrogel combines a dAM-containing extracellular matrix scaffold with chamomile-derived bioactive compounds, creating a favorable microenvironment for tissue repair. The addition of chamomile extract to the dAM-containing scaffold was associated with improved wound closure and tissue regeneration. While the present study design does not permit a definitive assessment of synergy between dAM and chamomile, these findings support the potential of this formulation as a multifunctional biomaterial platform for advanced wound healing applications.