Bioactive Biomaterials: Phenolic and Terpenic Compounds as Prospective Antibacterial and Antioxidant Additives for Electrospun Scaffolds

The application of electrospun scaffolds for musculoskeletal tissue repair, such as bone or tendon/ligament, is a growing field of research. They can mimic the fibrous architecture of native extracellular matrix, while simultaneously allowing to support cell attachment, proliferation, and ultimately tissue regeneration. However, implantation of electrospun scaffolds also faces the challenges of implant-associated infection or excessive oxidative stress. Both scenarios can result in serious inflammation, or fibrosis in the case of tendon injury repair, which might lead to failure of the implanted scaffold and strictly limited success of tissue healing. Modification of electrospun scaffolds via incorporation of compounds exerting antibacterial as well as antioxidant activity emerges as a promising approach to counteract these challenges. In this context, naturally derived compounds, such as those of phenolic or terpenic origin, are interesting candidates, because of their potential dual-action nature. In the first part of this review, the most promising candidate compounds to be incorporated into electrospun scaffolds for musculoskeletal tissue repair are examined. We discuss the mechanisms through which these compounds interact with Gram-positive and Gram-negative bacteria in regards to surface attachment, biofilm formation and virulence activity in general. We also highlight the most recent research on their antioxidant potential as well as their effect on cellular host inflammation pathways. In the second part of this review, particular emphasis is placed on strategies for incorporating these compounds into electrospun scaffolds. Finally, we propose future perspectives for research and development of functionalized electrospun scaffolds with bioactive character to advance translation into clinical application.