Abstract

The decellularization of plant-based biomaterials to generate tissue-engineered substitutes or in vitro cellular models has significantly increased in recent years. These vegetal tissues can be sourced from plant leaves and stems or fruits and vegetables, making them a low-cost, accessible, and sustainable resource from which to generate three-dimensional scaffolds. Each construct is distinct, representing a wide range of architectural and mechanical properties as well as innate vasculature networks. Based on the rapid rise in interest, this review aims to detail the current state of the art and presents the future challenges and perspectives of these unique biomaterials. First, we consider the different existing decellularization techniques, including chemical, detergent-free, enzymatic, and supercritical fluid approaches that are used to generate such scaffolds and examine how these protocols can be selected based on plant cellularity. We next examine strategies for cell seeding onto the plant-derived constructs and the importance of the different functionalization methods used to assist in cell adhesion and promote cell viability. Finally, we discuss how their structural features, such as inherent vasculature, porosity, morphology, and mechanical properties (i.e., stiffness, elasticity, etc.) position plant-based scaffolds as a unique biomaterial and drive their use for specific downstream applications. The main challenges in the field are presented throughout the discussion, and future directions are proposed to help improve the development and use of vegetal constructs in biomedical research.

Highlights

  • We evaluate the key advantages of vegetal material, including its natural and prefabricated vasculature, its specific architectural and mechanical properties, and we propose new ways in which it can be utilized for biological research

  • It has been demonstrated that a variety of cell types, including human endothelial cells [34,57,62], human dermal fibroblasts (HDFs) [35,58,62,65], human skeletal myoblasts [56], human cancer cell lines [32,55,70], human aortic smooth muscle cells [64], mesenchymal stem cells [34,35,54,64], human-induced pluripotent stem cells [52,63], and hiPSC-derived cardiomyocytes [34], as well as mouse fibroblasts [32,53,64] and mouse myoblasts [32,56] (Figure 3a,b), can attach and survive on a variety of decellularized plant scaffolds for periods of several weeks

  • As plants display a variety of stiffnesses and diverse topographies, these bio-inspired scaffolds recapitulate numerous mechanical aspects of the in vivo microenvironment that are vital for reproducing key tissue responses, as they greatly influence cell behavior

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Summary

Vegetal Scaffolds Are New Players to the Broader Field of Tissue Engineering

The field of tissue engineering (TE) combines materials science with cell biology to produce biological substitutes that restore tissue or organ function [1,2,3,4]. In recent years, several studies have started to use decellularized vegetal scaffolds to provide structural and biomechanical support for recellularization with mammalian cells, paving the way for the use of plant material for generating large (vascularized) tissue grafts [32,33,34,35]. As this unique area has expanded over the past few years [36], the purpose of this review is to discuss recent insights into the field. Sci. 2021, 22, 12347 confusion, an exhaustive list that specifies the formal scientific names is provided at the end of the manuscript

Alternative Strategies to Current Chemical Decellularization Protocol
Limitations
Decellularized Vegetal Tissues Support Cell Culture
The Exploitation of the Inherent Vegetal Vein Network to Provide a Unique
Biocompatibility Demonstration and the First In Vivo Applications
Additional Considerations for Decellularized Plant-Based Biomaterials
Findings
Conclusions
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