Faster and Protective Wound Healing Mechanistic of Para‐Coumaric Acid Loaded Liver ECM Scaffold Cross‐linked with Acellular Marine Kelp

Abstract Decellularized liver‐derived extracellular matrix is a unique combination of a complex milieu of growth factors and proteins that stimulate biochemical, physical, and mechanical cues to the cells. However, the lack of mechanical strength hindering the applicability of extracellular matrix (ECM) is an outstanding challenge. Herein, to deal with this problem, decellularized kelp is introduced as a crosslinking material thereby strengthening the physical structure of ECM for its utilization as a wound‐healing material. Consequently, a significant architectural change is observed in the ECM by forming a solid‐shaped scaffold. Nevertheless, the hindrance of high pH is addressed by incorporating the acidic drug p ‐coumaric acid. To evaluate the innate regenerative abilities, the scaffolds are applied to rat excisional wounds. A remarkable wound healing capability is demonstrated by both the EK scaffolds, but a faster regeneration is achieved with only EK‐20@cou. The speculated hypothesis is that the incorporation of p ‐coumaric acid can offer many additional bioactive benefits to the scaffold such as remarkable biocompatibility, antioxidant, and anti‐bacterial properties that are deliberately supported by the in vitro results. In silico molecular simulations (MS) validated that p ‐Cou released from the EK‐20@Cou scaffold is accountable for the observed extraordinary regenerative behavior as compared to EK‐20(PW).