Engineering vascular grafts from decellularized plants: Advances and challenges.

Small-caliber vascular grafts (<6 mm diameter) are critical for coronary and peripheral bypass surgeries, yet developing functional substitutes remains challenging. Autologous vessels are ideal but often unavailable or of poor quality. Synthetic grafts, such as expanded polytetrafluoroethylene (ePTFE) and Dacron, have high failure rates in small diameters due to thrombosis, intimal hyperplasia, and compliance mismatch. Tissue-engineered vascular grafts (TEVGs) aim to overcome these issues by providing a biocompatible scaffold with an endothelial lining. Decellularized plant tissues have recently gained attention as natural scaffolds for TEVGs due to their structural similarity to human vasculature. Leaves and stems provide an extracellular matrix (ECM) primarily composed of cellulose, which is biocompatible, porous, and non-thrombogenic. These scaffolds are cost-effective, scalable, and ethically uncontroversial. Decellularized parsley stems or leatherleaf leaves, for instance, can be recellularized with endothelial and smooth muscle cells (SMCs) to create small-diameter grafts that support endothelialization and withstand physiological pressures. Perfusion bioreactors further enhance the functionality of plant-based grafts by simulating physiological conditions. Pulsatile flow and pressure stimulate endothelial cell alignment, reducing thrombogenicity, while mechanical stimulation promotes SMC maturation and ECM deposition, improving graft strength and compliance. This review summarizes recent advances in plant-based vascular grafts and perfusion bioreactor conditioning, compares their performance to conventional grafts, and highlights remaining challenges. Decellularized plant scaffolds, with their inherent vascular architecture and biocompatibility, show promise as natural templates for small-caliber vascular grafts. However, further research is needed to address key challenges such as standardization, mechanical optimization, and long-term validation to facilitate their clinical application.